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European Heart Journal ESC GUIDELINES


doi:10.1093/eurheartj/ehw128

2016 ESC Guidelines for the diagnosis and


treatment of acute and chronic heart failure
The Task Force for the diagnosis and treatment of acute and chronic
heart failure of the European Society of Cardiology (ESC)

Developed with the special contribution of the Heart Failure


Association (HFA) of the ESC
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Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland),


8

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Adriaan A. Voors* (Co-Chairperson) (The Netherlands), Stefan D. Anker (Germany),


%

Hector Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK),


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Volkmar Falk (Germany), Jose Ramon Gonzalez-Juanatey (Spain), Veli-Pekka Harjola -


,

(Finland), Ewa A. Jankowska (Poland), Mariell Jessup (USA), Cecilia Linde (Sweden),
/

Petros Nihoyannopoulos (UK), John T. Parissis (Greece), Burkert Pieske (Germany),


,

Jillian P. Riley (UK), Giuseppe M. C. Rosano (UK/Italy), Luis M. Ruilope (Spain),


1 2

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Frank Ruschitzka (Switzerland), Frans H. Rutten (The Netherlands),


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Peter van der Meer (The Netherlands) 0

Document Reviewers: Gerasimos Filippatos (CPG Review Coordinator) (Greece), John J. V. McMurray (CPG Review
"

Coordinator) (UK), Victor Aboyans (France), Stephan Achenbach (Germany), Stefan Agewall (Norway), 


Nawwar Al-Attar (UK), John James Atherton (Australia), Johann Bauersachs (Germany), A. John Camm (UK),  

Scipione Carerj (Italy), Claudio Ceconi (Italy), Antonio Coca (Spain), Perry Elliott (UK), etin Erol (Turkey), !

"

Justin Ezekowitz (Canada), Covadonga Fernandez-Golfn (Spain), Donna Fitzsimons (UK), Marco Guazzi (Italy),
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* Corresponding authors: Piotr Ponikowski, Department of Heart Diseases, Wroclaw Medical University, Centre for Heart Diseases, Military Hospital, ul. Weigla 5, 50-981 Wroclaw, (
'

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Poland, Tel: +48 261 660 279, Tel/Fax: +48 261 660 237, E-mail: piotrponikowski@4wsk.pl. )

Adriaan Voors, Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands, Tel: +31 50 3612355, +

Fax: +31 50 3614391, E-mail: a.a.voors@umcg.nl.


ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix.
ESC entities having participated in the development of this document:
Associations: Acute Cardiovascular Care Association (ACCA), European Association for Cardiovascular Prevention and Rehabilitation (EACPR), European Association of
Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA).
Councils: Council on Cardiovascular Nursing and Allied Professions, Council for Cardiology Practice, Council on Cardiovascular Primary Care, Council on Hypertension.
Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Myocardial and Pericardial Diseases, Myocardial Function, Pulmonary Circulation and Right Ventricular
Function, Valvular Heart Disease.
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC
Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford
University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oup.com).
Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at
the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recom-
mendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encour-
aged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or
therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and
accurate decisions in consideration of each patients health condition and in consultation with that patient and, where appropriate and/or necessary, the patients caregiver. Nor
do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent
public health authorities, in order to manage each patients case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the
health professionals responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.
The article has been co-published with permission in European Heart Journal and European Journal of Heart Failure. All rights reserved in respect of European Heart Journal.
& European Society of Cardiology 2016. All rights reserved. For permissions please email: journals.permissions@oup.com.
Page 2 of 85 ESC Guidelines

Maxime Guenoun (France), Gerd Hasenfuss (Germany), Gerhard Hindricks (Germany), Arno W. Hoes
(The Netherlands), Bernard Iung (France), Tiny Jaarsma (Sweden), Paulus Kirchhof (UK/Germany), Juhani Knuuti
(Finland), Philippe Kolh (Belgium), Stavros Konstantinides (Germany/Greece), Mitja Lainscak (Slovenia),
Patrizio Lancellotti (Belgium), Gregory Y. H. Lip (UK), Francesco Maisano (Switzerland), Christian Mueller
(Switzerland), Mark C. Petrie (UK), Massimo F. Piepoli (Italy), Silvia G. Priori (Italy), Adam Torbicki (Poland),
Hiroyuki Tsutsui (Japan), Dirk J. van Veldhuisen (The Netherlands), Stephan Windecker (Switzerland), Clyde Yancy
(USA), Jose Luis Zamorano (Spain)

The disclosure forms of all experts involved in the development of these guidelines are available on the ESC website
http://www.escardio.org/guidelines.

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Keywords Guidelines Heart failure Natriuretic peptides Ejection fraction Diagnosis Pharmacotherapy
Neuro-hormonal antagonists Cardiac resynchronization therapy Mechanical circulatory support
Transplantation Arrhythmias Co-morbidities Hospitalization Multidisciplinary management

Table of Contents 7

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Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . 3 5.9 Cardiac computed tomography . . . . . . . . . . . . . . . . . 16 6

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1. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 5.10 Other diagnostic tests . . . . . . . . . . . . . . . . . . . . . . 17 

2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 5.10.1 Genetic testing in heart failure . . . . . . . . . . . . . . 17


4

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3. Definition, epidemiology and prognosis . . . . . . . . . . . . . . . 8 6. Delaying or preventing the development of overt heart ,

3.1 Definition of heart failure . . . . . . . . . . . . . . . . . . . . . 8 failure or preventing death before the onset of symptoms . . . . . 18
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3.2 Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 7. Pharmacological treatment of heart failure with reduced




3.2.1 Heart failure with preserved, mid-range and reduced ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 

ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 7.1 Objectives in the management of heart failure . . . . . . . 19


!

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3.2.2 Terminology related to the time course of heart 7.2 Treatments recommended in all symptomatic patients 4

"

failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 with heart failure with reduced ejection fraction . . . . . . . . . 20


5

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3.2.3 Terminology related to the symptomatic severity 7.2.1 Angiotensin-converting enzyme inhibitors . . . . . . . 20 0

of heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 7.2.2 Beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . . 20 6

"

3.3 Epidemiology, aetiology and natural history of heart failure 10 7.2.3 Mineralocorticoid/aldosterone receptor antagonists . 20
0

3.4 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 7.3 Other treatments recommended in selected symptomatic 

 

4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 patients with heart failure with reduced ejection fraction . . . 20 

4.1 Symptoms and signs . . . . . . . . . . . . . . . . . . . . . . . . 10 7.3.1 Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20


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4.2 Essential initial investigations: natriuretic peptides, 7.3.2 Angiotensin receptor neprilysin inhibitor . . . . . . . . 23 $

electrocardiogram, and echocardiography . . . . . . . . . . . . . 11 7.3.3 If - channel inhibitor . . . . . . . . . . . . . . . . . . . . . . 24


 &

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4.3 Algorithm for the diagnosis of heart failure . . . . . . . . . 12 7.3.4 Angiotensin II type I receptor blockers . . . . . . . . . 24
&

4.3.1 Algorithm for the diagnosis of heart failure in the 7.3.5 Combination of hydralazine and isosorbide *

non-acute setting . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 dinitrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24


4.3.2 Diagnosis of heart failure with preserved ejection 7.4 Other treatments with less certain benefits in
fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 symptomatic patients with heart failure with reduced ejection
5. Cardiac imaging and other diagnostic tests . . . . . . . . . . . . . 14 fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.1 Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 7.4.1 Digoxin and other digitalis glycosides . . . . . . . . . . 24
5.2 Transthoracic echocardiography . . . . . . . . . . . . . . . . 14 7.4.2 n-3 polyunsaturated fatty acids . . . . . . . . . . . . . . 25
5.2.1 Assessment of left ventricular systolic function . . . . 14 7.5 Treatments not recommended (unproven benefit) in
5.2.2 Assessment of left ventricular diastolic function . . . 15 symptomatic patients with heart failure with reduced ejection
5.2.3 Assessment of right ventricular function and fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
pulmonary arterial pressure . . . . . . . . . . . . . . . . . . . . 15 7.5.1 3-Hydroxy-3-methylglutaryl-coenzyme A reductase
5.3 Transoesophageal echocardiography . . . . . . . . . . . . . 15 inhibitors (statins) . . . . . . . . . . . . . . . . . . . . . . . . . . 25
5.4 Stress echocardiography . . . . . . . . . . . . . . . . . . . . . 15 7.5.2 Oral anticoagulants and antiplatelet therapy . . . . . . 25
5.5 Cardiac magnetic resonance . . . . . . . . . . . . . . . . . . . 15 7.5.3 Renin inhibitors . . . . . . . . . . . . . . . . . . . . . . . . 25
5.6 Single-photon emission computed tomography and 7.6 Treatments not recommended (believed to cause harm)
radionuclide ventriculography . . . . . . . . . . . . . . . . . . . . . 15 in symptomatic patients with heart failure with reduced
5.7 Positron emission tomography . . . . . . . . . . . . . . . . . 15 ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
5.8 Coronary angiography . . . . . . . . . . . . . . . . . . . . . . . 16 7.6.1 Calcium-channel blockers . . . . . . . . . . . . . . . . . . 26
ESC Guidelines Page 3 of 85

8. Non-surgical device treatment of heart failure with reduced 12. Acute heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 12.1 Definition and classification . . . . . . . . . . . . . . . . . . . 43
8.1 Implantable cardioverter-defibrillator . . . . . . . . . . . . . 26 12.2 Diagnosis and initial prognostic evaluation . . . . . . . . . 44
8.1.1 Secondary prevention of sudden cardiac death . . . . 26 12.3 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
8.1.2 Primary prevention of sudden cardiac death . . . . . . 27 12.3.1 Identification of precipitants/causes leading to
8.2 Cardiac resynchronization therapy . . . . . . . . . . . . . . . 28 decompensation that needs urgent management . . . . . . . 48
8.3 Other implantable electrical devices . . . . . . . . . . . . . . 29 12.3.2 Criteria for hospitalization in ward vs intensive
9. Treatment of heart failure with preserved ejection fraction . . 29 care/coronary care unit . . . . . . . . . . . . . . . . . . . . . . . 49
9.1 Effect of treatment on symptoms in heart failure with 12.3.3 Management of the early phase . . . . . . . . . . . . . 49
preserved ejection fraction . . . . . . . . . . . . . . . . . . . . . . . 30 12.3.4 Management of patients with cardiogenic shock . . 54
9.2 Effect of treatment on hospitalization for heart failure in 12.4 Management of evidence-based oral therapies . . . . . . 54
heart failure with preserved ejection fraction . . . . . . . . . . . 30 12.5 Monitoring of clinical status of patients hospitalized due
9.3 Effect of treatment on mortality in heart failure with to acute heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . 55
preserved ejection fraction . . . . . . . . . . . . . . . . . . . . . . . 30 12.6 Criteria for discharge from hospital and follow-up in
9.4 Other considerations . . . . . . . . . . . . . . . . . . . . . . . 30 high-risk period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
10. Arrhythmias and conductance disturbances . . . . . . . . . . . . 30 12.7 Goals of treatment during the different stages of
10.1 Atrial fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . 31 management of acute heart failure . . . . . . . . . . . . . . . . . . 55
10.1.1 Prevention of atrial fibrillation in patients with heart 13. Mechanical circulatory support and heart transplantation . . . 56 7

"

failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 13.1 Mechanical circulatory support . . . . . . . . . . . . . . . . 56 8

10.1.2 Management of new-onset, rapid atrial fibrillation in 13.1.1 Mechanical circulatory support in acute heart
6

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patients with heart failure . . . . . . . . . . . . . . . . . . . . . . 31 failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 

10.1.3 Rate control . . . . . . . . . . . . . . . . . . . . . . . . . 31 13.1.2 Mechanical circulatory support in end-stage chronic 0

"

10.1.4 Rhythm control . . . . . . . . . . . . . . . . . . . . . . . 32 heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 ,

10.1.5 Thromboembolism prophylaxis . . . . . . . . . . . . . 33 13.2 Heart transplantation . . . . . . . . . . . . . . . . . . . . . . . 58


- .

10.2 Ventricular arrhythmias . . . . . . . . . . . . . . . . . . . . . 33 14. Multidisciplinary team management . . . . . . . . . . . . . . . . . 59




10.3 Symptomatic bradycardia, pauses and 14.1 Organization of care . . . . . . . . . . . . . . . . . . . . . . . 59 

atrio-ventricular block . . . . . . . . . . . . . . . . . . . . . . . . . . 34 14.2 Discharge planning . . . . . . . . . . . . . . . . . . . . . . . . 61


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11. Co-morbidities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 14.3 Lifestyle advice . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 4

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11.1 Heart failure and co-morbidities . . . . . . . . . . . . . . . 35 14.4 Exercise training . . . . . . . . . . . . . . . . . . . . . . . . . . 61


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11.2 Angina and coronary artery disease . . . . . . . . . . . . . 35 14.5 Follow-up and monitoring . . . . . . . . . . . . . . . . . . . . 61 0

11.2.1 Pharmacological management . . . . . . . . . . . . . . 35 14.6 The older adult, frailty and cognitive impairment . . . . . 62
6

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11.2.2 Myocardial revascularization . . . . . . . . . . . . . . . 35 14.7 Palliative and end-of-life care . . . . . . . . . . . . . . . . . . 62 

11.3 Cachexia and sarcopenia (for frailty, please refer to 15. Gaps in evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 

 

Section 14) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 16. To do and not to messages from the Guidelines . . . . . . . . . 64 

11.4 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 17. Web Addenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 "

11.5 Central nervous system (including depression, stroke and 18. Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
$

autonomic dysfunction) . . . . . . . . . . . . . . . . . . . . . . . . . 37 19. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66


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11.6 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
&

11.7 Erectile dysfunction . . . . . . . . . . . . . . . . . . . . . . . . 38 *

11.8 Gout and arthritis . . . . . . . . . . . . . . . . . . . . . . . . . 38 Abbreviations and acronyms


11.9 Hypokalaemia and hyperkalaemia . . . . . . . . . . . . . . . 38
11.10 Hyperlipidaemia . . . . . . . . . . . . . . . . . . . . . . . . . 38 ACC/AHA American College of Cardiology/American
11.11 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Heart Association
11.12 Iron deficiency and anaemia . . . . . . . . . . . . . . . . . . 39 ACCF/AHA American College of Cardiology Foundation/
11.13 Kidney dysfunction (including chronic kidney disease, American Heart Association
acute kidney injury, cardio-renal syndrome, and prostatic ACE angiotensin-converting enzyme
obstruction) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 ACEI angiotensin-converting enzyme inhibitor
11.14 Lung disease (including asthma and chronic obstructive ACS acute coronary syndrome
pulmonary disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 AF atrial fibrillation
11.15 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 AHF acute heart failure
11.16 Sleep disturbance and sleep-disordered AHI apnoea/hypopnoea index
breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 AIDS acquired immunodeficiency syndrome
11.17 Valvular heart disease . . . . . . . . . . . . . . . . . . . . . . 42 AKI acute kidney injury
11.17.1 Aortic stenosis . . . . . . . . . . . . . . . . . . . . . . . 42 Aldo-DHF aldosterone receptor blockade in diastolic
11.17.2 Aortic regurgitation . . . . . . . . . . . . . . . . . . . . 42 heart failure
11.17.3 Mitral regurgitation . . . . . . . . . . . . . . . . . . . . 42 AL amyloid light chain
11.17.4 Tricuspid regurgitation . . . . . . . . . . . . . . . . . . 42 ALT alanine aminotransferase
Page 4 of 85 ESC Guidelines

AMI acute myocardial infarction CHARM-Preserved Candesartan Cilexetil in Heart Failure Assess-
AMICA Atrial fibrillation Management In Congestive ment of Reduction in Mortality and Morbidity
heart failure with Ablation CI cardiac index
ANP A-type natriuretic peptide CI-AKI contrast-induced acute kidney injury
ANS autonomic nervous system CIBIS II Cardiac Insufficiency Bisoprolol Study II
ARB angiotensin receptor blocker CK creatine kinase
ARNI angiotensin receptor neprilysin inhibitor CKD chronic kidney disease
ARVC arrhythmogenic right ventricular CK-MB creatine kinase MB
cardiomyopathy CMP cardiomyopathy
AST aspartate aminotransferase CMR cardiac magnetic resonance
ASV assisted servo-ventilation COMPANION Comparison of Medical Therapy, Pacing, and
ATLAS Assessment of Treatment with Lisinopril And Defibrillation in Heart Failure
Survival CONFIRM-HF Ferric CarboxymaltOse evaluatioN on per-
ATTR transthyretin-mediated amyloidosis Formance in patients with IRon deficiency
AV atrio-ventricular in coMbination with chronic Heart Failure
AVP arginine vasopressin CONSENSUS Cooperative North Scandinavian Enalapril
b.i.d. bis in die (twice daily) Survival Study
BioPACE Biventricular Pacing for Atrio-ventricular COPD chronic obstructive pulmonary disease 7

"

Block to Prevent Cardiac Desynchronization COPERNICUS Carvedilol Prospective Randomized Cumula-


8

BiPAP bilevel positive airway pressure tive Survival


"

BiVAD biventricular assist device COX-2 inhibitor cyclooxygenase-2 inhibitor




BLOCK-HF Biventricular versus Right Ventricular Pacing in CPAP continuous positive airway pressure
0

"

Heart Failure Patients with Atrio-ventricular CPG Committee for Practice Guidelines ,

Block CRT cardiac resynchronization therapy


- .

BMI body mass index CRT-D defibrillator with cardiac resynchronization 0

BNP B-type natriuretic peptide therapy 

BP blood pressure CRT-P pacemaker with cardiac resynchronization


1 2

"

bpm beats per minute therapy 4

"

BSA body surface area CSA central sleep apnoea 1

"

BTB bridge to bridge CSR Cheyne-Stokes respiration


0

BTC bridge to candidacy CT computed tomography 2

"

BTD bridge to decision CYP3A4 cytochrome P450 3A4




BTR bridge to recovery DCM dilated cardiomyopathy




 

BTT bridge to transplantation DES desmin 

BUN blood urea nitrogen DHA docosahexaenoic acid "

CABANA Catheter ABlation versus ANtiarrhythmic DIG-PEF ancillary Digitalis Investigation Group trial
$

 &

drug therapy for Atrial fibrillation DNA deoxyribonucleic acid '

&

CABG coronary artery bypass graft/grafting DOSE Diuretic Optimization Strategies Evaluation
(

CAD coronary artery disease DPD 3,3-diphosphono-1,2-propanodicarboxylic *

CARE-HF CArdiac REsynchronization in Heart Failure acid


CASTLE-AF Catheter Ablation versus Standard conven- DPP4i dipeptidyl peptidase-4 inhibitor
tional Treatment in patients with LEft ven- DT destination therapy
tricular dysfunction and Atrial Fibrillation e early diastolic tissue velocity
CCB calcium-channel blocker ECG electrocardiogram
CCM cardiac contractility modulation Echo-CRT Echocardiography Guided Cardiac Resyn-
CCS Canadian Cardiovascular Society chronization Therapy
CCU coronary care unit ECLS extracorporeal life support
CHA2DS2-VASc Congestive heart failure or left ventricular dys- ECMO extracorporeal membrane oxygenation
function, Hypertension, Age 75 (doubled), ED emergency department
Diabetes, Stroke (doubled)-Vascular disease, EF ejection fraction
Age 6574, Sex category (female) eGFR estimated glomerular filtration rate
CHARM-Alternative Candesartan in heart failure assessment of EHRA European Heart Rhythm Association
reduction in mortality and morbidity EMA European Medicines Agency
CHARM-Added Candesartan Cilexetil in Heart Failure Assess- EMB endomyocardial biopsy
ment of Reduction in Mortality and Morbidity EMF endomyocardial fibrosis
ESC Guidelines Page 5 of 85

EMPHASIS-HF Eplerenone in Mild Patients Hospitalization IVRT isovolumetric relaxation time


and Survival Study in Heart Failure KCCQ Kansas City Cardiomyopathy Questionnaire
EPA eicosapentaenoic acid LA left atrial/atrium
EPHESUS Eplerenone Post-Acute Myocardial Infarction LAE left atrial enlargement
Heart Failure Efficacy and Survival Study LAVI left atrial volume index
ESC European Society of Cardiology LBBB left bundle branch block
EU European Union LGE late gadolinium enhancement
EULAR European League Against Rheumatism LMNA lamin A/C
Ex-DHF Exercise training in Diastolic Heart Failure LMWH low-molecular-weight heparin
FACIT-Pal Functional Assessment of Chronic Illness LV left ventricular/left ventricle
Therapy - Palliative Care LVAD left ventricular assist device
FAIR-HF Ferinject Assessment in Patients with Iron LVEDP left ventricular end diastolic pressure
Deficiency and Chronic Heart Failure LVEDV left ventricular end diastolic volume
FCM ferric carboxymaltose LVEF left ventricular ejection fraction
FiO2 fraction of inspired oxygen LVESV left ventricular end systolic volume
GFR glomerular filtration rate LVID left ventricular internal dimension
GGTP gamma-glutamyl transpeptidase LVMI left ventricular mass index
GH growth hormone LVSD left ventricular systolic dysfunction 7

"

GLS global longitudinal strain MADIT-CRT Multicenter Automatic Defibrillator Implant-


8

GLP-1 glucagon-like peptide 1 ation Trial with Cardiac Resynchronization


"

HAS-BLED Hypertension, Abnormal renal/liver function Therapy




(1 point each), Stroke, Bleeding history or MCS mechanical circulatory support


0

"

predisposition, Labile international normal- MERIT-HF Metoprolol CR/XL Randomised Intervention ,

ized ratio, Elderly (.65 years), Drugs/alcohol Trial in Congestive Heart Failure
- .

concomitantly (1 point each) MR mineralocorticoid receptor/magnetic 0

HbA1c glycated haemoglobin resonance 

HCM hypertrophic cardiomyopathy MRA mineralocorticoid receptor antagonist


1 2

"

HES hypereosinophilic syndrome MR-proANP mid-regional pro A-type natriuretic peptide 4

"

HF heart failure MV mitral valve 1

"

HFA Heart Failure Association MV A-Wave mitral valve late diastolic flow
0

HFmrEF heart failure with mid-range ejection fraction MV E-Wave mitral valve early diastolic flow 2

"

HFpEF heart failure with preserved ejection fraction MYBPC3 cardiac myosin binding protein C


HFrEF heart failure with reduced ejection fraction MYH7 cardiac b-myosin heavy chain


 

H-ISDN hydralazine and isosorbide dinitrate n-3 PUFA n-3 polyunsaturated fatty acid 

HIV/AIDS human immunodeficiency virus/acquired NEP neprilysin "

immune deficiency syndrome NOAC non-vitamin K antagonist oral anticoagulant


$

 &

HR heart rate NP natriuretic peptide '

&

Hs troponin high sensitivity troponin NPPV non-invasive positive pressure ventilation


(

IABP intra-aortic balloon pump NSAID non-steroidal anti-inflammatory drug *

IABP-SHOCK IntraAortic Balloon Pump in Cardiogenic Shock NSTE-ACS non-ST elevation acute coronary syndrome
IABP-SHOCK II IntraAortic Balloon Pump in Cardiogenic NT-proBNP N-terminal pro-B type natriuretic peptide
Shock II NYHA New York Heart Association
ICD implantable cardioverter-defibrillator o.d. omne in die (once daily)
ICU intensive care unit OMT optimal medical therapy
IHD ischaemic heart disease OSA obstructive sleep apnoea
IL interleukin PaCO2 partial pressure of carbon dioxide in arterial
INH Interdisciplinary Network for Heart Failure blood
INTERMACS Interagency Registry for Mechanically PAH pulmonary arterial hypertension
Assisted Circulatory Support PaO2 partial pressure of oxygen in arterial blood
IN-TIME Implant-based multiparameter telemonitor- PARADIGM-HF Prospective Comparison of ARNI with ACEI
ing of patients with heart failure to Determine Impact on Global Mortality and
IPD individual patient data Morbidity in Heart Failure Trial
I-PRESERVE Irbesartan in Heart Failure with Preserved PARAMOUNT LCZ696 Compared to Valsartan in Patients
Ejection Fraction Study With Chronic Heart Failure and Preserved
i.v. intravenous Left-ventricular Ejection Fraction
IVC inferior vena cava PCI percutaneous coronary intervention
Page 6 of 85 ESC Guidelines

PCWP pulmonary capillary wedge pressure SpO2 transcutaneous oxygen saturation


PDE5I phosphodiesterase 5 inhibitor SPPB Short Physical Performance Battery
Peak VO2 peak oxygen uptake SPRINT Systolic Blood Pressure Intervention
PEP-CHF Perindopril in Elderly People with Chronic Trial
Heart Failure STEMI ST segment elevation myocardial
PET positron emission tomography infarction
PLN phospholamban STICH Surgical Treatment for Ischemic Heart
PPV positive pressure ventilation Failure
PRISMA 7 seven-item, self-completion questionnaire to STS structured telephone support
identify older adults with moderate to severe TAPSE tricuspid annular plane systolic excursion
disabilities TAVI transaortic valve implantation
PROTECT II Prospective, Multi-center, Randomized TDI tissue Doppler imaging
Controlled Trial of the IMPELLA RECOVER TECOS Trial Evaluating Cardiovascular Outcomes
LP 2.5 System Versus Intra Aortic Balloon with Sitagliptin
Pump (IABP) in Patients Undergoing Non TEHAF Telemonitoring in Patients with Heart
Emergent High Risk PCI Failure
PS-PEEP pressure-support positive end-expiratory Tele-HF Telemonitoring to Improve Heart
pressure Failure Outcomes 7

"

PV pulmonary vein TIA transient ischaemic attack


8

PVR pulmonary vascular resistance TIBC total iron-binding capacity


"

QALY quality-adjusted life year t.i.d. ter in die (three times a day)


QRS Q, R, and S waves (combination of three of TIM-HF Telemedical Interventional Monitoring in


0

"

the graphical deflections) Heart Failure ,

RA right atrium/atrial TOE transoesophageal echocardiography


- .

RAAS renin angiotensin aldosterone system TOPCAT Treatment of Preserved Cardiac Function 0

RAFT Resynchronization-Defibrillation for Ambu- Heart Failure with an Aldosterone 

latory Heart Failure Trial Antagonist


1 2

"

RALES Randomized Aldactone Evaluation Study TR tricuspid regurgitation 4

"

RCT randomized controlled trial TRV tricuspid regurgitation velocity 1

"

RELAX Phosphodiesterase-5 Inhibition to Improve TSAT transferrin saturation


0

Clinical Status and Exercise Capacity in TSH thyroid-stimulating hormone 2

"

Diastolic Heart Failure TTE transthoracic echocardiography




REVERSE REsynchronization reVErses Remodeling in TTN titin




 

Systolic left vEntricular dysfunction ULT urate lowering therapy 

RV right ventricular/ventricle VAD ventricular assist device "

RVAD right ventricular assist device Val-HeFT Valsartan Heart Failure Trial
$

 &

SADHART Sertraline Antidepressant Heart Attack VE-VCO2 ventilatory equivalent ratio for carbon '

&

Randomized Trial dioxide


(

SAVE Survival After Veno-arterial ECMO VT ventricular tachycardia *

SBP systolic blood pressure VV interval interventricular pacing interval


SCD-HeFT Sudden Cardiac Death in Heart Failure Trial WBC white blood cells
SDB sleep-disordered breathing WISH Weight Monitoring in Patients with Severe
SENIORS Study of the Effects of Nebivolol Intervention Heart Failure
on Outcomes and Rehospitalisations in WRF worsening renal function
Seniors with Heart Failure
SERVE-HF Treatment of sleep-disordered breathing 1. Preamble
with predominant central sleep apnoea with
adaptive Servo-ventilation in patients with Guidelines summarize and evaluate all available evidence on a par-
chronic heart failure ticular issue at the time of the writing process, with the aim of assist-
SHIFT Systolic Heart failure treatment with the If ing health professionals in selecting the best management strategies
inhibitor ivabradine Trial for an individual patient with a given condition, taking into account
SIGNIFY Study Assessing the Morbidity Mortality the impact on outcome, as well as the riskbenefit ratio of particular
Benefits of the I f Inhibitor Ivabradine in diagnostic or therapeutic means. Guidelines and recommendations
Patients with Coronary Artery Disease should help health professionals to make decisions in their daily
SOLVD Studies of Left Ventricular Dysfunction practice. However, the final decisions concerning an individual pa-
SPECT single-photon emission computed tient must be made by the responsible health professional(s) in con-
tomography sultation with the patient and caregiver as appropriate.
ESC Guidelines Page 7 of 85

A great number of Guidelines have been issued in recent years by panels. The Committee is also responsible for the endorsement pro-
the European Society of Cardiology (ESC) as well as by other soci- cess of these Guidelines. The ESC Guidelines undergo extensive re-
eties and organisations. Because of the impact on clinical practice, view by the CPG and external experts. After appropriate revisions
quality criteria for the development of guidelines have been estab- the Guidelines are approved by all the experts involved in the Task
lished in order to make all decisions transparent to the user. The re- Force. The finalized document is approved by the CPG for publica-
commendations for formulating and issuing ESC Guidelines can be tion in the European Heart Journal. The Guidelines were developed
found on the ESC website (http://www.escardio.org/Guidelines- after careful consideration of the scientific and medical knowledge
&-Education/Clinical-Practice-Guidelines/Guidelines-development/ and the evidence available at the time of their dating.
Writing-ESC-Guidelines). ESC Guidelines represent the official pos- The task of developing ESC Guidelines covers not only integration
ition of the ESC on a given topic and are regularly updated. of the most recent research, but also the creation of educational tools
Members of this Task Force were selected by the ESC to re- and implementation programmes for the recommendations. To im-
present professionals involved with the medical care of patients plement the guidelines, condensed pocket guidelines versions, sum-
with this pathology. Selected experts in the field undertook a com- mary slides, booklets with essential messages, summary cards for
prehensive review of the published evidence for management (in- non-specialists, and an electronic version for digital applications
cluding diagnosis, treatment, prevention and rehabilitation) of a (smartphones, etc.) are produced. These versions are abridged and
given condition according to ESC Committee for Practice Guide- thus, if needed, one should always refer to the full text version, which
lines (CPG) policy. A critical evaluation of diagnostic and therapeutic is freely available on the ESC website. The National Cardiac Societies
procedures was performed, including assessment of the risk-benefit of the ESC are encouraged to endorse, translate and implement all 7

"

ratio. Estimates of expected health outcomes for larger populations ESC Guidelines. Implementation programmes are needed because 8

were included, where data exist. The level of evidence and the
6

"

strength of the recommendation of particular management options 

were weighed and graded according to predefined scales, as out- 0

"

Table 1.2 Level of evidence 9

lined in Tables 1.1 and 1.2. ,

The experts of the writing and reviewing panels provided declara-


- .

tions of interest forms for all relationships that might be perceived as




real or potential sources of conflicts of interest. These forms were 

compiled into one file and can be found on the ESC website (http://
!

1 2

"

www.escardio.org/guidelines). Any changes in declarations of interest 4

"

that arise during the writing period must be notified to the ESC and
5

"

updated. The Task Force received its entire financial support from the 0

ESC without any involvement from the healthcare industry.


6

"

The ESC CPG supervises and coordinates the preparation of new 

Guidelines produced by task forces, expert groups or consensus 

 

"

Table 1.1 Classes of recommendations 


%

&

'

&

+
Page 8 of 85 ESC Guidelines

it has been shown that the outcome of disease may be favourably in- (viii) a new algorithm for a combined diagnosis and treatment ap-
fluenced by the thorough application of clinical recommendations. proach of acute HF based on the presence/absence of conges-
Surveys and registries are needed to verify that real-life daily prac- tion/hypoperfusion.
tice is in keeping with what is recommended in the guidelines, thus
We followed the format of the previous ESC 2012 HF Guidelines.
completing the loop between clinical research, writing of guidelines,
Therapeutic recommendations state the treatment effect supported
disseminating them and implementing them into clinical practice.
by the class and level of recommendation in tabular format; in the
Health professionals are encouraged to take the ESC Guidelines
case of chronic HF due to left ventricular systolic dysfunction
fully into account when exercising their clinical judgment, as well as
(LVSD) the recommendations focus on mortality and morbidity
in the determination and the implementation of preventive, diagnos-
outcomes. Detailed summaries of the key evidence supporting gen-
tic or therapeutic medical strategies. However, the ESC Guidelines
erally recommended treatments have been provided. For diagnostic
do not override in any way whatsoever the individual responsibility
recommendations a level of evidence C has been typically decided
of health professionals to make appropriate and accurate decisions
upon, because for the majority of diagnostic tests there are no data
in consideration of each patients health condition and in consult-
from randomized controlled trials (RCTs) showing that they will
ation with that patient and the patients caregiver where appropriate
lead to reductions in morbidity and/or mortality. Practical guidance
and/or necessary. It is also the health professionals responsibility to
is provided for the use of the important disease-modifying drugs and
verify the rules and regulations applicable to drugs and devices at the
diuretics. When possible, other relevant guidelines, consensus
time of prescription.
statements and position papers have been cited to avoid unduly
7

lengthy text. All tables should be read in conjunction with their ac- "

companying text and not read in isolation. #

"

This document is the result of extensive interactions between the


%

2. Introduction
5

Task Force, the review team and the ESC Committee for Practice
5

"

The aim of all the ESC Guidelines is to help health professionals to Guidelines. It represents a consensus of opinion of all of the experts 9

make decisions in their everyday life based on the best available evi- involved in its development. Concurrently to the development of -
!

dence. We will soon be celebrating the 30th anniversary of clinical the 2016 ESC Guidelines on HF, the group writing the 2016 /

trials that for the first time incontrovertibly demonstrated that the ACC/AHA/HFSA Focused Update on New Pharmacological Ther- 0

apy for Heart Failure independently developed its recommenda-


%

miserable outcome of patients with heart failure (HF) can be mark- 1


0

edly improved.2 Since then, in the area of HF management we have tions on new pharmacotherapy for Heart Failure. Both working
"

groups/Task Force independently surveyed the evidence, arrived


"

witnessed and celebrated numerous highs, which have definitely 1


0

at similar conclusions, and constructed similar, but not identical, re-


"

outnumbered several lows, all of which have allowed us to unravel 0

the pathophysiology of this clinical syndrome, but more importantly commendations. Given the concordance, the respective organiza- %

has led to better care of our patients.3 In the year 2016, no one tions simultaneously issued aligned recommendations on the use "

of these new treatments to minimize confusion and improve the


/

would any longer dispute that, by applying all evidence-based dis- 




coveries, HF is now becoming a preventable and treatable disease. care of patients with HF.  

The aim of this document is to provide practical, evidence-based !

"

guidelines for the diagnosis and treatment of HF. The principal


#

changes from the 2012 guidelines relate to: 3. Definition, epidemiology and 
%

&

(i) a new term for patients with HF and a left ventricular ejection prognosis (
'

&

fraction (LVEF) that ranges from 40 to 49% HF with mid- *

range EF (HFmrEF); we believe that identifying HFmrEF as a 3.1 Definition of heart failure
separate group will stimulate research into the underlying char- HF is a clinical syndrome characterized by typical symptoms
acteristics, pathophysiology and treatment of this population; (e.g. breathlessness, ankle swelling and fatigue) that may be accom-
(ii) clear recommendations on the diagnostic criteria for HF with re- panied by signs (e.g. elevated jugular venous pressure, pulmonary
duced EF (HFrEF), HFmrEF and HF with preserved EF (HFpEF); crackles and peripheral oedema) caused by a structural and/or func-
(iii) a new algorithm for the diagnosis of HF in the non-acute set- tional cardiac abnormality, resulting in a reduced cardiac output and/
ting based on the evaluation of HF probability; or elevated intracardiac pressures at rest or during stress.
(iv) recommendations aimed at prevention or delay of the devel- The current definition of HF restricts itself to stages at which clinical
opment of overt HF or the prevention of death before the on- symptoms are apparent. Before clinical symptoms become apparent,
set of symptoms; patients can present with asymptomatic structural or functional cardiac
(v) indications for the use of the new compound sacubitril/ abnormalities [systolic or diastolic left ventricular (LV) dysfunction],
valsartan, the first in the class of angiotensin receptor neprily- which are precursors of HF. Recognition of these precursors is import-
sin inhibitors (ARNIs); ant because they are related to poor outcomes, and starting treatment
(vi) modified indications for cardiac resynchronization therapy at the precursor stage may reduce mortality in patients with asymp-
(CRT); tomatic systolic LV dysfunction4,5 (for details see Section 6).
(vii) the concept of an early initiation of appropriate therapy going Demonstration of an underlying cardiac cause is central to the
along with relevant investigations in acute HF that follows the diagnosis of HF. This is usually a myocardial abnormality causing sys-
time to therapy approach already well established in acute tolic and/or diastolic ventricular dysfunction. However, abnormal-
coronary syndrome (ACS); ities of the valves, pericardium, endocardium, heart rhythm and
ESC Guidelines Page 9 of 85

conduction can also cause HF (and more than one abnormality is of- characteristics, pathophysiology and treatment of this group of pa-
ten present). Identification of the underlying cardiac problem is cru- tients. Patients with HFmrEF most probably have primarily mild sys-
cial for therapeutic reasons, as the precise pathology determines the tolic dysfunction, but with features of diastolic dysfunction
specific treatment used (e.g. valve repair or replacement for valvular (Table 3.1).
disease, specific pharmacological therapy for HF with reduced EF, Patients without detectable LV myocardial disease may have
reduction of heart rate in tachycardiomyopathy, etc). other cardiovascular causes for HF (e.g. pulmonary hypertension,
valvular heart disease, etc.). Patients with non-cardiovascular path-
ologies (e.g. anaemia, pulmonary, renal or hepatic disease) may have
3.2 Terminology
symptoms similar or identical to those of HF and each may compli-
3.2.1 Heart failure with preserved, mid-range and reduced
cate or exacerbate the HF syndrome.
ejection fraction
The main terminology used to describe HF is historical and is based
on measurement of the LVEF. HF comprises a wide range of pa- 3.2.2 Terminology related to the time course of heart
tients, from those with normal LVEF [typically considered as failure
50%; HF with preserved EF (HFpEF)] to those with reduced In these guidelines, the term HF is used to describe the symptomatic
LVEF [typically considered as ,40%; HF with reduced EF (HFrEF)] syndrome, graded according to the New York Heart Association
(Table 3.1). Patients with an LVEF in the range of 40 49% represent (NYHA) functional classification (see Section 3.2.3 and Web
a grey area, which we now define as HFmrEF (Table 3.1). Differen- Table 3.2), although a patient can be rendered asymptomatic by
7

tiation of patients with HF based on LVEF is important due to treatment. In these guidelines, a patient who has never exhibited "

different underlying aetiologies, demographics, co-morbidities and the typical symptoms and/or signs of HF and with a reduced LVEF #

"

response to therapies.6 Most clinical trials published after 1990 se- is described as having asymptomatic LV systolic dysfunction. Patients
%

lected patients based on LVEF [usually measured using echocardiog- who have had HF for some time are often said to have chronic HF.
5

"

raphy, a radionuclide technique or cardiac magnetic resonance A treated patient with symptoms and signs that have remained gen- 9

(CMR)], and it is only in patients with HFrEF that therapies have erally unchanged for at least 1 month is said to be stable. If chronic -
!

been shown to reduce both morbidity and mortality. stable HF deteriorates, the patient may be described as decompen- /

The diagnosis of HFpEF is more challenging than the diagnosis of sated and this may happen suddenly or slowly, often leading to hos- 0

HFrEF. Patients with HFpEF generally do not have a dilated LV, but pital admission, an event of considerable prognostic importance.
%

1 2

instead often have an increase in LV wall thickness and/or increased New-onset (de novo) HF may also present acutely, for example,
"

left atrial (LA) size as a sign of increased filling pressures. Most have as a consequence of acute myocardial infarction (AMI), or in a sub-
"

additional evidence of impaired LV filling or suction capacity, also acute (gradual) fashion, for example, in patients with a dilated cardio-
"

classified as diastolic dysfunction, which is generally accepted as myopathy (DCM), who often have symptoms for weeks or months %

the likely cause of HF in these patients (hence the term diastolic before the diagnosis becomes clear. Although symptoms and signs 
"

HF). However, most patients with HFrEF (previously referred to of HF may resolve, the underlying cardiac dysfunction may not, and
/

as systolic HF) also have diastolic dysfunction, and subtle abnormal- patients remain at the risk of recurrent decompensation.  

ities of systolic function have been shown in patients with HFpEF. Occasionally, however, a patient may have HF due to a problem !

"

Hence the preference for stating preserved or reduced LVEF over that resolves completely (e.g. acute viral myocarditis, takotsubo car- #

preserved or reduced systolic function. diomyopathy or tachycardiomyopathy). Other patients, particularly 


%

&

In previous guidelines it was acknowledged that a grey area exists those with idiopathic DCM, may also show substantial or even (
'

&

between HFrEF and HFpEF.7 These patients have an LVEF that complete recovery of LV systolic function with modern disease- )

ranges from 40 to 49%, hence the term HFmrEF. Identifying HFmrEF modifying therapy [including angiotensin-converting enzyme inhibi-
+

as a separate group will stimulate research into the underlying tor (ACEI), beta-blocker, mineralocorticoid receptor antagonist

Table 3.1 Definition of heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction
(HFrEF)

BNP B-type natriuretic peptide; HF heart failure; HFmrEF heart failure with mid-range ejection fraction; HFpEF heart failure with preserved ejection fraction; HFrEF
heart failure with reduced ejection fraction; LAE left atrial enlargement; LVEF left ventricular ejection fraction; LVH left ventricular hypertrophy; NT-proBNP N-terminal
pro-B type natriuretic peptide.
a
Signs may not be present in the early stages of HF (especially in HFpEF) and in patients treated with diuretics.
b
BNP.35 pg/ml and/or NT-proBNP.125 pg/mL.
Page 10 of 85 ESC Guidelines

(MRA), ivabradine and/or CRT]. Congestive HF is a term that is In clinical practice, a clear distinction between acquired and inher-
sometimes used, and may describe acute or chronic HF with evi- ited cardiomyopathies remains challenging. In most patients with a
dence of volume overload. Many or all of these terms may be accur- definite clinical diagnosis of HF, there is no confirmatory role for
ately applied to the same patient at different times, depending upon routine genetic testing, but genetic counselling is recommended in
their stage of illness. patients with hypertrophic cardiomyopathy (HCM), idiopathic
DCM or arrhythmogenic right ventricular cardiomyopathy
3.2.3 Terminology related to the symptomatic severity (ARVC) (see Section 5.10.1), since the outcomes of these tests
of heart failure may have clinical implications.
The NYHA functional classification (Web Table 3.2) has been used Over the last 30 years, improvements in treatments and their im-
to describe the severity of symptoms and exercise intolerance. plementation have improved survival and reduced the hospitalization
However, symptom severity correlates poorly with many measures rate in patients with HFrEF, although the outcome often remains un-
of LV function; although there is a clear relationship between the se- satisfactory. The most recent European data (ESC-HF pilot study)
verity of symptoms and survival, patients with mild symptoms may demonstrate that 12-month all-cause mortality rates for hospitalized
still have an increased risk of hospitalization and death.8 10 and stable/ambulatory HF patients were 17% and 7%, respectively,
Sometimes the term advanced HF is used to characterize pa- and the 12-month hospitalization rates were 44% and 32%, respect-
tients with severe symptoms, recurrent decompensation and severe ively.35 In patients with HF (both hospitalized and ambulatory), most
cardiac dysfunction.11 The American College of Cardiology Founda- deaths are due to cardiovascular causes, mainly sudden death and
tion/American Heart Association (ACCF/AHA) classification de- worsening HF. All-cause mortality is generally higher in HFrEF than 7

HFpEF.35,36 Hospitalizations are often due to non-cardiovascular


"

scribes stages of HF development based on structural changes and


8

symptoms (Web Table 3.3).12 The Killip classification may be used to causes, particularly in patients with HFpEF. Hospitalization for cardio-
6

"

describe the severity of the patients condition in the acute setting vascular causes did not change from 2000 to 2010, whereas those 

with non-cardiovascular causes increased.31


4

after myocardial infarction (see Section 12).13


0

"

3.4 Prognosis
,

- .

3.3 Epidemiology, aetiology and natural Estimation of prognosis for morbidity, disability and death helps pa-
/

history of heart failure tients, their families and clinicians decide on the appropriate type
,

and timing of therapies (in particular, decisions about a rapid transi-


0

1 2

The prevalence of HF depends on the definition applied, but is ap- "

tion to advanced therapies) and assists with planning of health and


3

proximately 12% of the adult population in developed countries,


4

"

social services and resources.


0

rising to 10% among people .70 years of age.14 17 Among peo-


1

"

Numerous prognostic markers of death and/or HF hospitalization


ple .65 years of age presenting to primary care with breathlessness
0

have been identified in patients with HF (Web Table 3.5). However, 6

on exertion, one in six will have unrecognized HF (mainly


2

"

their clinical applicability is limited and precise risk stratification in 0

HFpEF).18,19 The lifetime risk of HF at age 55 years is 33% for




HF remains challenging.


men and 28% for women.16 The proportion of patients with HFpEF


 

In recent decades, several multivariable prognostic risk scores


ranges from 22 to 73%, depending on the definition applied, the clin- 

have been developed for different populations of patients with !

ical setting (primary care, hospital clinic, hospital admission), age and
"

HF,36 41 and some are available as interactive online applications.


#

sex of the studied population, previous myocardial infarction and %

Multivariable risk scores may help predict death in patients with  &

the year of publication.17,18,20 30


HF, but remain less useful for the prediction of subsequent HF hos-
'

&

Data on temporal trends based on hospitalized patients suggest


(

pitalizations.37,38 A systematic review examining 64 prognostic


)

that the incidence of HF may be decreasing, more for HFrEF than


*

models37 along with a meta-analysis and meta-regression study of


for HFpEF.31,32 HFpEF and HFrEF seem to have different epidemio-
117 prognostic models38 revealed only a moderate accuracy of
logical and aetiological profiles. Compared with HFrEF, patients
models predicting mortality, whereas models designed to predict
with HFpEF are older, more often women and more commonly
the combined endpoint of death or hospitalization, or only hospital-
have a history of hypertension and atrial fibrillation (AF), while a his-
ization, had an even poorer discriminative ability.
tory of myocardial infarction is less common.32,33 The characteristics
of patients with HFmrEF are between those with HFrEF and HFpEF,34
but further studies are needed to better characterize this population. 4. Diagnosis
The aetiology of HF is diverse within and among world regions.
There is no agreed single classification system for the causes of 4.1 Symptoms and signs
HF, with much overlap between potential categories (Table 3.4). Symptoms are often non-specific and do not, therefore, help discrim-
Many patients will have several different pathologiescardiovascu- inate between HF and other problems (Table 4.1).42 46 Symptoms and
lar and non-cardiovascularthat conspire to cause HF. Identifica- signs of HF due to fluid retention may resolve quickly with diuretic
tion of these diverse pathologies should be part of the diagnostic therapy. Signs, such as elevated jugular venous pressure and displace-
workup, as they may offer specific therapeutic opportunities. ment of the apical impulse, may be more specific, but are harder to
Many patients with HF and ischaemic heart disease (IHD) have a detect and have poor reproducibility.18,46,47 Symptoms and signs
history of myocardial infarction or revascularization. However, a may be particularly difficult to identify and interpret in obese indivi-
normal coronary angiogram does not exclude myocardial scar duals, in the elderly and in patients with chronic lung disease.48 50
(e.g. by CMR imaging) or impaired coronary microcirculation as al- Younger patients with HF often have a different aetiology, clinical pres-
ternative evidence for IHD. entation and outcome compared with older patients.51,52
ESC Guidelines Page 11 of 85

Table 3.4 Aetiologies of heart failure

DISEASED MYOCARDIUM
Ischaemic heart Myocardial scar
disease
Myocardial stunning/hibernation
Epicardial coronary artery disease
Abnormal coronary microcirculation
Endothelial dysfunction
Toxic damage Recreational substance abuse Alcohol, cocaine, amphetamine, anabolic steroids.
Heavy metals Copper, iron, lead, cobalt.
Medications Cytostatic drugs (e.g. anthracyclines), immunomodulating drugs (e.g. interferons monoclonal
antibodies such as trastuzumab, cetuximab), antidepressant drugs, antiarrhythmics, non-steroidal

Radiation
Immune-mediated Related to infection Bacteria, spirochaetes, fungi, protozoa, parasites (Chagas disease), rickettsiae, viruses (HIV/AIDS).
Not related to infection Lymphocytic/giant cell myocarditis, autoimmune diseases (e.g. Graves disease, rheumatoid
damage
arthritis, connective tissue disorders, mainly systemic lupus erythematosus), hypersensitivity and 7

eosinophilic myocarditis (ChurgStrauss). "

Related to malignancy #

"

Not related to malignancy Amyloidosis, sarcoidosis, haemochromatosis (iron), glycogen storage diseases (e.g. Pompe disease), 5

lysosomal storage diseases (e.g. Fabry disease). 5

Metabolic Hormonal
"

derangements disease, Addison disease, diabetes, metabolic syndrome, phaeochromocytoma, pathologies related ,

to pregnancy and peripartum.


!

- .

Nutritional


(e.g. malignancy, AIDS, anorexia nervosa), obesity. ,

Genetic abnormalities Diverse forms HCM, DCM, LV non-compaction, ARVC, restrictive cardiomyopathy (for details see respective
0

1 2

expert documents), muscular dystrophies and laminopathies.


"

"

ABNORMAL LOADING CONDITIONS 1


0

"

Hypertension 0

Valve and Acquired Mitral, aortic, tricuspid and pulmonary valve diseases.
%

myocardium "

Congenital Atrial and ventricular septum defects and others (for details see a respective expert document). 0

structural defects


Pericardial and Pericardial Constrictive pericarditis  

endomyocardial Pericardial effusion 

pathologies !

Endomyocardial "

High output states %

 &

Volume overload '

&

ARRHYTHMIAS )

Tachyarrhythmias Atrial, ventricular arrhythmias. +

Bradyarrhythmias Sinus node dysfunctions, conduction disorders.

ARVC arrhythmogenic right ventricular cardiomyopathy; DCM dilated cardiomyopathy; EMF endomyocardial fibrosis; GH growth hormone; HCM hypertrophic
cardiomyopathy; HES hypereosinophilic syndrome; HIV/AIDS human immunodeficiency virus/acquired immune deficiency syndrome; LV left ventricular.

A detailed history should always be obtained. HF is unusual in an 4.2 Essential initial investigations:
individual with no relevant medical history (e.g. a potential cause of natriuretic peptides, electrocardiogram
cardiac damage), whereas certain features, particularly previous
myocardial infarction, greatly increase the likelihood of HF in a pa-
and echocardiography
tient with appropriate symptoms and signs.42 45 The plasma concentration of natriuretic peptides (NPs) can be used
At each visit, symptoms and signs of HF need to be assessed, with as an initial diagnostic test, especially in the non-acute setting when
particular attention to evidence of congestion. Symptoms and signs echocardiography is not immediately available. Elevated NPs help
are important in monitoring a patients response to treatment and establish an initial working diagnosis, identifying those who require
stability over time. Persistence of symptoms despite treatment usu- further cardiac investigation; patients with values below the cut-
ally indicates the need for additional therapy, and worsening of point for the exclusion of important cardiac dysfunction do not
symptoms is a serious development (placing the patient at risk of ur- require echocardiography (see also Section 4.3 and Section 12).
gent hospital admission and death) and merits prompt medical Patients with normal plasma NP concentrations are unlikely to
attention. have HF. The upper limit of normal in the non-acute setting for
Page 12 of 85 ESC Guidelines

Echocardiography is the most useful, widely available test in pa-


Table 4.1 Symptoms and signs typical of heart failure tients with suspected HF to establish the diagnosis. It provides im-
mediate information on chamber volumes, ventricular systolic and
Symptoms Signs
diastolic function, wall thickness, valve function and pulmonary
Typical hypertension.65 74 This information is crucial in establishing the
Breathlessness Elevated jugular venous pressure diagnosis and in determining appropriate treatment (see Sections
Orthopnoea 5.2 5.4 for details on echocardiography).
Paroxysmal nocturnal dyspnoea Third heart sound (gallop rhythm)
The information provided by careful clinical evaluation and the
Reduced exercise tolerance Laterally displaced apical impulse
Fatigue, tiredness, increased time above mentioned tests will permit an initial working diagnosis and
to recover after exercise treatment plan in most patients. Other tests are generally required
Ankle swelling only if the diagnosis remains uncertain (e.g. if echocardiographic
Less typical images are suboptimal or an unusual cause of HF is suspected)
Nocturnal cough Weight gain (>2 kg/week) (for details see Sections 5.5 5.10).
Wheezing Weight loss (in advanced HF)
Bloated feeling Tissue wasting (cachexia)
Loss of appetite Cardiac murmur
Confusion (especially in the Peripheral oedema (ankle, sacral, 4.3 Algorithm for the diagnosis of heart
elderly) scrotal) failure
Depression Pulmonary crepitations 4.3.1 Algorithm for the diagnosis of heart failure in the
7

Palpitations Reduced air entry and dullness to


"

Dizziness percussion at lung bases (pleural


non-acute setting #

An algorithm for the diagnosis of HF in the non-acute setting is


"

Syncope effusion)
%

Bendopnea53 Tachycardia shown in Figure 4.1. The diagnosis of HF in the acute setting is 5

Irregular pulse discussed in Section 12.


0

"

Tachypnoea
Cheyne Stokes respiration
For patients presenting with symptoms or signs for the first time, ,

- .

Hepatomegaly non-urgently in primary care or in a hospital outpatient clinic /

Ascites (Table 4.1), the probability of HF should first be evaluated based 0

Cold extremities on the patients prior clinical history [e.g. coronary artery disease


Oliguria 1
!

Narrow pulse pressure


(CAD), arterial hypertension, diuretic use], presenting symptoms "

(e.g. orthopnoea), physical examination (e.g. bilateral oedema, in-


4

"

creased jugular venous pressure, displaced apical beat) and resting


1

"

HF heart failure. 0

ECG. If all elements are normal, HF is highly unlikely and other diag- #

noses need to be considered. If at least one element is abnormal,


2

"

B-type natriuretic peptide (BNP) is 35 pg/mL and for N-terminal plasma NPs should be measured, if available, to identify those


pro-BNP (NT-proBNP) it is 125 pg/mL; in the acute setting, higher who need echocardiography (an echocardiogram is indicated if


 

values should be used [BNP , 100 pg/mL, NT-proBNP , 300 pg/ the NP level is above the exclusion threshold or if circulating NP 

mL and mid-regional pro A-type natriuretic peptide (MR-proANP) levels cannot be assessed).55 60,75 78
"

, 120 pmol/L]. Diagnostic values apply similarly to HFrEF and


$

HFpEF; on average, values are lower for HFpEF than for HFrEF.54,55
 &

At the mentioned exclusionary cut-points, the negative predictive 4.3.2 Diagnosis of heart failure with preserved ejection (
'

&

fraction )

values are very similar and high (0.94 0.98) in both the non-acute *

The diagnosis of HFpEF remains challenging. LVEF is normal and


and acute setting, but the positive predictive values are lower
signs and symptoms for HF (Table 4.1) are often non-specific and
both in the non-acute setting (0.44 0.57) and in the acute setting
do not discriminate well between HF and other clinical conditions.
(0.66 0.67).54,56 61 Therefore, the use of NPs is recommended
This section summarizes practical recommendations necessary for
for ruling-out HF, but not to establish the diagnosis.
proper diagnosis of this clinical entity in clinical practice.
There are numerous cardiovascular and non-cardiovascular
The diagnosis of chronic HFpEF, especially in the typical elderly
causes of elevated NPs that may weaken their diagnostic utility in
patient with co-morbidities and no obvious signs of central fluid
HF. Among them, AF, age and renal failure are the most important
overload, is cumbersome and a validated gold standard is missing.
factors impeding the interpretation of NP measurements.55 On the
To improve the specificity of diagnosing HFpEF, the clinical diagnosis
other hand, NP levels may be disproportionally low in obese pa-
needs to be supported by objective measures of cardiac dysfunction
tients62 (see also Section 12.2 and Table 12.3).
at rest or during exercise. The diagnosis of HFpEF requires the fol-
An abnormal electrocardiogram (ECG) increases the likelihood
lowing conditions to be fulfilled (see Table 3.1):
of the diagnosis of HF, but has low specificity.18,46,63,64 Some abnor-
malities on the ECG provide information on aetiology (e.g. myocar- The presence of symptoms and/or signs of HF (see Table 4.1)
dial infarction), and findings on the ECG might provide indications A preserved EF (defined as LVEF 50% or 40 49% for
for therapy (e.g. anticoagulation for AF, pacing for bradycardia, HFmrEF)
CRT if broadened QRS complex) (see Sections 8 and 10). HF is un- Elevated levels of NPs (BNP .35 pg/mL and/or NT-proBNP
likely in patients presenting with a completely normal ECG (sensitiv- .125 pg/mL)
ity 89%).43 Therefore, the routine use of an ECG is mainly Objective evidence of other cardiac functional and structural al-
recommended to rule out HF. terations underlying HF (for details, see below)
ESC Guidelines Page 13 of 85

"

"

"

- .

1 2

"

"

"

"

 

"

 &

'

&

Figure 4.1 Diagnostic algorithm for a diagnosis of heart failure of non-acute onset
BNP B-type natriuretic peptide; CAD coronary artery disease; HF heart failure; MI myocardial infarction; NT-proBNP N-terminal
pro-B type natriuretic peptide.
a
Patient reporting symptoms typical of HF (see Table 4.1).
b
Normal ventricular and atrial volumes and function.
c
Consider other causes of elevated natriuretic peptides (Table 12.3).
Page 14 of 85 ESC Guidelines

In case of uncertainty, a stress test or invasively measured ele- Patients with HFpEF are a heterogeneous group with various
vated LV filling pressure may be needed to confirm the diagnosis underlying aetiologies and pathophysiological abnormalities. Based
(for details, see below). on specific suspected causes, additional tests can be performed
(Web Table 4.4).71,88 94 However, they can only be recommended
The initial assessment consists of a clinical diagnosis compatible with if the results might affect management.
the algorithm presented above and the assessment of LVEF by echo-
cardiography. The cut-off of 50% for a diagnosis of HFpEF is arbi-
trary; patients with an LVEF between 40 and 49% are often 5. Cardiac imaging and other
classified as HFpEF in clinical trials.79 However, in the present guide- diagnostic tests
lines, we define HFpEF as an LVEF 50% and consider patients with
an LVEF between 40 and 49% as a grey area, which could be indi- Cardiac imaging plays a central role in the diagnosis of HF and in guiding
cated as HFmrEF. Clinical signs and symptoms are similar for pa- treatment. Of several imaging modalities available, echocardiography is
tients with HFrEF, HFmrEF and HFpEF. Typical demographics and the method of choice in patients with suspected HF, for reasons of ac-
co-morbidities are provided in Web Table 4.2. The resting ECG curacy, availability (including portability), safety and cost.68,69,72 Echocar-
may reveal abnormalities such as AF, LV hypertrophy and repolari- diography may be complemented by other modalities, chosen
sation abnormalities. A normal ECG and/or plasma concentrations according to their ability to answer specific clinical questions and taking
of BNP ,35 pg/mL and/or NT-proBNP ,125 pg/mL make a diag- account of contraindications to and risks of specific tests.71,73
nosis of HFpEF, HFmrEF or HFrEF unlikely. In general, imaging tests should only be performed when they 7

The next step comprises an advanced workup in case of initial evi- have a meaningful clinical consequence. The reliability of the out- "

comes is highly dependent on the imaging modality, the operator


#

dence of HFpEF/HFmrEF and consists of objective demonstration of


6

"

structural and/or functional alterations of the heart as the underlying and centre experience and imaging quality. Normal values may 5

cause for the clinical presentation. Key structural alterations are a vary with age, sex and imaging modality. 4

"

left atrial volume index (LAVI) .34 mL/m2 or a left ventricular ,

mass index (LVMI) 115 g/m 2 for males and 95 g/m 2 for fe- 5.1 Chest X-ray -
!

males.65,67,72 Key functional alterations are an E/e 13 and a


/

A chest X-ray is of limited use in the diagnostic work-up of patients




mean e septal and lateral wall ,9 cm/s.65,67,70,72,80 84 Other (indir- with suspected HF. It is probably most useful in identifying an alter-
,

ect) echocardiographically derived measurements are longitudinal native, pulmonary explanation for a patients symptoms and signs, 1
!

"

strain or tricuspid regurgitation velocity (TRV).72,82 An overview i.e. pulmonary malignancy and interstitial pulmonary disease, al-
3

"

of normal and abnormal values for echocardiographic parameters though computed tomography (CT) of the chest is currently the 1
5

"

related to diastolic function is presented in Web Table 4.3. Not all standard of care. For the diagnosis of asthma or chronic obstructive 0

of the recommended values are identical to those published in pre- pulmonary disease (COPD), pulmonary function testing with spir- 6

"

vious guidelines, because of the inclusion of new data published in ometry is needed. The chest X-ray may, however, show pulmonary
0

recent reports, in particular by Cabarello et al. 70 venous congestion or oedema in a patient with HF, and is more


helpful in the acute setting than in the non-acute setting.49,64 It is im-


 

A diastolic stress test can be performed with echocardiography, 

portant to note that significant LV dysfunction may be present with-


!

typically using a semi-supine bicycle ergometer exercise protocol "

with assessment of LV (E/e ) and pulmonary artery pressures out cardiomegaly on the chest X-ray.49,64 $

(TRV), systolic dysfunction (longitudinal strain), stroke volume and


 &

cardiac output changes with exercise.85,86 Different dynamic exercise 5.2 Transthoracic echocardiography
'

&

protocols are available, with semi-supine bicycle ergometry and echo- Echocardiography is a term used here to refer to all cardiac ultra- *

cardiography at rest and submaximal exercise being used most of- sound imaging techniques, including two-dimensional/three-
ten.85 Exercise-induced increases in E/e beyond diagnostic cut-offs dimensional echocardiography, pulsed and continuous wave Dop-
(i.e. .13), but also other indirect measures of systolic and diastolic pler, colour flow Doppler, tissue Doppler imaging (TDI) contrast
function, such as longitudinal strain or TRV, are used. Alternatively, in- echocardiography and deformation imaging (strain and strain rate).
vasive haemodynamics at rest with assessment of filling pressures Transthoracic echocardiography (TTE) is the method of choice
[pulmonary capillary wedge pressure (PCWP) 15 mmHg or left for assessment of myocardial systolic and diastolic function of
ventricular end diastolic pressure (LVEDP) 16 mmHg] followed both left and right ventricles.
by exercise haemodynamics if below these thresholds, with assess-
ment of changes in filling pressures, pulmonary artery systolic pres- 5.2.1 Assessment of left ventricular systolic function
sure, stroke volume and cardiac output, can be performed.87 For measurement of LVEF, the modified biplane Simpsons rule is re-
The diagnosis of HFpEF in patients with AF is difficult. Since AF is commended. LV end diastolic volume (LVEDV) and LV end systolic
associated with higher NP levels, the use of NT-proBNP or BNP for volume (LVESV) are obtained from apical four- and two-chamber
diagnosing HFpEF probably needs to be stratified by the presence of views. This method relies on accurate tracing of endocardial bor-
sinus rhythm (with lower cut-offs) vs. AF (higher cut-offs). LAVI is ders. In case of poor image quality, contrast agents should be
increased by AF, and functional parameters of diastolic dysfunction used to improve endocardial delineation.72 Measurement of region-
are less well established in AF, and other cut-off values probably ap- al wall motion abnormalities might be particularly relevant for pa-
ply. On the other hand, AF might be a sign of the presence of HFpEF, tients suspected of CAD or myocarditis.
and patients with AF and HFpEF often have similar patient character- The Teichholz and Quinones methods of calculating LVEF from
istics. In addition, patients with HFpEF and AF might have more ad- linear dimensions, as well as a measurement of fractional shortening,
vanced HF compared with patients with HFpEF and sinus rhythm. are not recommended, as they may result in inaccuracies,
ESC Guidelines Page 15 of 85

particularly in patients with regional LV dysfunction and/or LV re- 5.4 Stress echocardiography
modelling. Three-dimensional echocardiography of adequate quality Exercise or pharmacological stress echocardiography may be used
improves the quantification of LV volumes and LVEF and has the for the assessment of inducible ischaemia and/or myocardium viabil-
best accuracy compared with values obtained through CMR.95 ity99 and in some clinical scenarios of patients with valve disease (e.g.
Doppler techniques allow the calculation of haemodynamic vari- dynamic mitral regurgitation, low-flow low-gradient aortic sten-
ables, such as stroke volume index and cardiac output, based on the osis).99,100 There are also suggestions that stress echocardiography
velocity time integral at the LV outflow tract area. may allow the detection of diastolic dysfunction related to exercise
In recent years, tissue Doppler parameters (S wave) and deform- exposure in patients with exertional dyspnoea, preserved LVEF and
ation imaging techniques (strain and strain rate) have been shown to inconclusive diastolic parameters at rest.85,86
be reproducible and feasible for clinical use, especially in detecting sub-
tle abnormalities in systolic function in the preclinical stage; however, 5.5 Cardiac magnetic resonance
measurements may vary among vendors and software versions.74
CMR is acknowledged as the gold standard for the measurements of
volumes, mass and EF of both the left and right ventricles. It is the
5.2.2 Assessment of left ventricular diastolic function best alternative cardiac imaging modality for patients with non-
LV diastolic dysfunction is thought to be the underlying pathophysio- diagnostic echocardiographic studies (particularly for imaging of
logical abnormality in patients with HFpEF and perhaps HFmrEF, and the right heart) and is the method of choice in patients with complex
thus its assessment plays an important role in diagnosis. Although congenital heart diseases.91,101,102
echocardiography is at present the only imaging technique that can CMR is the preferred imaging method to assess myocardial fibrosis
7

"

allow for the diagnosis of diastolic dysfunction, no single echocardiog-


8

using late gadolinium enhancement (LGE) along with T1 mapping and #

raphy variable is sufficiently accurate to be used in isolation to make a


"

can be useful for establishing HF aetiology.91,103 For example, CMR


%

diagnosis of LV diastolic dysfunction. Therefore, a comprehensive with LGE allows differentiation between ischaemic and non-ischaemic
5

echocardiography examination incorporating all relevant two- origins of HF and myocardial fibrosis/scars can be visualized. In addition,
"

dimensional and Doppler data is recommended (see Section 4.3.2). CMR allows the characterization of myocardial tissue of myocarditis,
,

- .

amyloidosis, sarcoidosis, Chagas disease, Fabry disease non-compaction /

5.2.3 Assessment of right ventricular function and cardiomyopathy and haemochromatosis.91,101,103,104 0

pulmonary arterial pressure CMR may also be used for the assessment of myocardial ischae- 1
%

An obligatory element of echocardiography examination is the as- mia and viability in patients with HF and CAD (considered suitable
"

sessment of right ventricle (RV) structure and function, including for coronary revascularization). However, limited evidence from
"

RV and right atrial (RA) dimensions, an estimation of RV systolic RCTs has failed to show that viability assessed by CMR or other
"

function and pulmonary arterial pressure. Among parameters re-


#

means identified patients who obtained clinical benefit from revas- %

flecting RV systolic function, the following measures are of particular cularization.105 107 "

importance: tricuspid annular plane systolic excursion (TAPSE; ab- Clinical limitations of CMR include local expertise, lower availability
/

normal TAPSE ,17 mm indicates RV systolic dysfunction) and and higher costs compared with echocardiography, uncertainty about  

tissue Doppler-derived tricuspid lateral annular systolic velocity




safety in patients with metallic implants (including cardiac devices) and !

(s ) (s velocity ,9.5 cm/s indicates RV systolic dysfunction).72,96


"

less reliable measurements in patients with tachyarrhythmias. Claus- #

Systolic pulmonary artery pressure is derived from an optimal trophobia is an important limitation for CMR. Linear gadolinium- 
%

&

recording of maximal tricuspid regurgitant jet and the tricuspid based contrast agents are contraindicated in individuals with a glom- '

&

systolic gradient, together with an estimate of RA pressure on the erular filtration rate (GFR) ,30 mL/min/1.73m2, because they may )

basis of inferior vena cava (IVC) size and its breathing-related col- trigger nephrogenic systemic fibrosis (this may be less of a concern
+

lapse.97 RV size should be routinely assessed by conventional two- with newer cyclic gadolinium-based contrast agents).108
dimensional echocardiography using multiple acoustic windows, and
the report should include both qualitative and quantitative para- 5.6 Single-photon emission computed
meters. In laboratories with experience in three-dimensional echo- tomography and radionuclide
cardiography, when knowledge of RV volumes may be clinically
ventriculography
important, three-dimensional measurement of RV volumes is re-
Single-photon emission CT (SPECT) may be useful in assessing is-
commended.95 Three-dimensional speckle tracking echocardio-
chaemia and myocardial viability.109 Gated SPECT can also yield in-
graphy may be an additional quantitative method to assess RV
formation on ventricular volumes and function, but exposes the
function in specialised centres.98
patient to ionizing radiation. 3,3-diphosphono-1,2-propanodicar-
boxylic acid (DPD) scintigraphy may be useful for the detection of
5.3 Transoesophageal echocardiography transthyretin cardiac amyloidosis.110
Transoesophageal echocardiography (TOE) is not needed in the
routine diagnostic assessment of HF; however, it may be valuable 5.7 Positron emission tomography
in some clinical scenarios of patients with valve disease, suspected Positron emission tomography (PET) (alone or with CT) may be
aortic dissection, suspected endocarditis or congenital heart disease used to assess ischaemia and viability, but the flow tracers (N-13
and for ruling out intracavitary thrombi in AF patients requiring car- ammonia or O-15 water) require an on-site cyclotron.92,111 Rubid-
dioversion. When the severity of mitral or aortic valve disease does ium is an alternative tracer for ischaemia testing with PET, which can
not match the patients symptoms using TTE alone, a TOE examin- be produced locally at relatively low cost. Limited availability, radi-
ation should be performed. ation exposure and cost are the main limitations.
Page 16 of 85 ESC Guidelines

5.8 Coronary angiography 5.9 Cardiac computed tomography


Indications for coronary angiography in patients with HF are in con- The main use of cardiac CT in patients with HF is as a non-invasive
cordance with the recommendations of other relevant ESC guide- means to visualize the coronary anatomy in patients with HF with
lines.112 114 Coronary angiography is recommended in patients low intermediate pre-test probability of CAD or those with equivo-
with HF who suffer from angina pectoris recalcitrant to medical cal non-invasive stress tests in order to exclude the diagnosis of
therapy,115 provided the patient is otherwise suitable for coronary CAD, in the absence of relative contraindications. However, the
revascularization. Coronary angiography is also recommended in test is only required when its results might affect a therapeutic
patients with a history of symptomatic ventricular arrhythmia or decision.
aborted cardiac arrest. Coronary angiography should be considered The most important clinical indications for the applicability of cer-
in patients with HF and intermediate to high pre-test probability of tain imaging methods in patients with suspected or confirmed HF
CAD and the presence of ischaemia in non-invasive stress tests in are shown in the recommendations table.
order to establish the ischaemic aetiology and CAD severity.

Recommendations for cardiac imaging in patients with suspected or established heart failure

Recommendations Class a Level b Ref c

TTE is recommended for the assessment of myocardial structure and function in subjects with suspected HF in order to establish 7

I C "

a diagnosis of either HFrEF, HFmrEF or HFpEF. 8

"

TTE is recommended to assess LVEF in order to identify patients with HF who would be suitable for evidence-based %

I C 5

pharmacological and device (ICD, CRT) treatment recommended for HFrEF.




"

TTE is recommended for the assessment of valve disease, right ventricular function and pulmonary arterial pressure in patients with 9

I C
an already established diagnosis of either HFrEF, HFmrEF or HFpEF in order to identify those suitable for correction of valve disease.
,

- .

TTE is recommended for the assessment of myocardial structure and function in subjects to be exposed to treatment which
/

I C
potentially can damage myocardium (e.g. chemotherapy).
0

Other techniques (including systolic tissue Doppler velocities and deformation indices, i.e. strain and strain rate), should be
!

1 2

IIa C "

considered in a TTE protocol in subjects at risk of developing HF in order to identify myocardial dysfunction at the preclinical stage.
3

"

CMR is recommended for the assessment of myocardial structure and function (including right heart) in subjects with poor
1

"

I C
acoustic window and patients with complex congenital heart diseases (taking account of cautions/contra-indications to CMR). 0

CMR with LGE should be considered in patients with dilated cardiomyopathy in order to distinguish between ischaemic and non- "

IIa C
0

ischaemic myocardial damage in case of equivocal clinical and other imaging data (taking account of cautions/contra-indications to CMR). /

CMR is recommended for the characterization of myocardial tissue in case of suspected myocarditis, amyloidosis, sarcoidosis,
 

Chagas disease, Fabry disease non-compaction cardiomyopathy, and haemochromatosis (taking account of cautions/contra- I C !

indications to CMR).
"

Non-invasive stress imaging (CMR, stress echocardiography, SPECT, PET) may be considered for the assessment of myocardial
%

 &

ischaemia and viability in patients with HF and CAD (considered suitable for coronary revascularization) before the decision on IIb B 116118 (
'

&

revascularization. )

Invasive coronary angiography is recommended in patients with HF and angina pectoris recalcitrant to pharmacological
therapy or symptomatic ventricular arrhythmias or aborted cardiac arrest (who are considered suitable for potential coronary I C
revascularization) in order to establish the diagnosis of CAD and its severity.

Invasive coronary angiography should be considered in patients with HF and intermediate to high pre-test probability of CAD and
the presence of ischaemia in non-invasive stress tests (who are considered suitable for potential coronary revascularization) in IIa C
order to establish the diagnosis of CAD and its severity.

Cardiac CT may be considered in patients with HF and low to intermediate pre-test probability of CAD or those with equivocal
IIb C
non-invasive stress tests in order to rule out coronary artery stenosis.

Reassessment of myocardial structure and function is recommended using non-invasive imaging:


- in patients presenting with worsening HF symptoms (including episodes of AHF) or experiencing any other
important cardiovascular event;
I C
- in patients with HF who have received evidence-based pharmacotherapy in maximal tolerated doses, before the decision on
device implantation (ICD, CRT);
- in patients exposed to therapies which may damage the myocardium (e.g. chemotherapy) (serial assessments).

AHF acute heart failure; CAD coronary artery disease; CMR cardiac magnetic resonance; CRT cardiac resynchronization therapy; CT computed tomography; HF
heart failure; HFpEF heart failure with preserved ejection fraction; HFmrEF heart failure with mid-range ejection fraction; HFrEF heart failure with reduced ejection fraction;
ICD implantable cardioverter-defibrillator; LGE late gadolinium enhancement; LVEF left ventricular ejection fraction; PET positron emission tomography; SPECT
single-photon emission computed tomography; TTE transthoracic echocardiography.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
ESC Guidelines Page 17 of 85

5.10 Other diagnostic tests sessments and endomyocardial biopsy. The major typical indications
Comprehensive assessment of patients with HF comprises, besides are summarized in the recommendations table for diagnostic tests in
medical history and physical examination, including adequate imaging patients with HF. Although there is extensive research on biomarkers
techniques, a set of additional diagnostic tests, i.e. laboratory vari- in HF (e.g. ST2, galectin 3, copeptin, adrenomedullin), there is no def-
ables, ECG, chest X-ray, exercise testing, invasive haemodynamic as- inite evidence to recommend them for clinical practice.

Recommendations for diagnostic tests in patients with heart failure

Recommendations Class a Level b Ref c

The following diagnostic tests are recommended/should be considered for initial assessment of a patient with newly diagnosed
HF in order to evaluate the patients suitability for particular therapies, to detect reversible/treatable causes of HF and co-
morbidities interfering with HF:
- haemoglobin and WBC
- sodium, potassium, urea, creatinine (with estimated GFR)
- liver function tests (bilirubin, AST, ALT, GGTP)
- glucose, HbA1c I C
7

"

- TSH 8

- ferritin, TSAT = TIBC 6

"

- natriuretic peptides C
5

IIa 

Additional diagnostic tests aiming to identify other HF aetiologies and comorbidities should be considered in individual "

IIa C
9

patients with HF when there is a clinical suspicion of a particular pathology (see Table 3.4 on HF aetiologies). ,

- .

A 12-lead ECG is recommended in all patients with HF in order to determine heart rhythm, heart rate, QRS morphology, and
/

I C


QRS duration, and to detect other relevant abnormalities. This information is needed to plan and monitor treatment. 0

Exercise testing in patients with HF:


0

1 2

"

- is recommended as a part of the evaluation for heart transplantation and/or mechanical circulatory support 3

I C 119, 120 4

"

(cardiopulmonary exercise testing); 1


0

- should be considered to optimize prescription of exercise training (preferably cardiopulmonary exercise testing); IIa C
"

- should be considered to identify the cause of unexplained dyspnoea (cardiopulmonary exercise testing). IIa C
#

- may be considered to detect reversible myocardial ischaemia. IIb C "

Chest radiography (X-ray) is recommended in patients with HF to detect/exclude alternative pulmonary or other diseases, 


which may contribute to dyspnoea. It may also identify pulmonary congestion/oedema and is more useful in patients with I C  

suspected HF in the acute setting.




"

Right heart catheterization with a pulmonary artery catheter: $

- is recommended in patients with severe HF being evaluated for heart transplantation or mechanical circulatory support; I C
%

 &

'

IIa C
&

pulmonary hypertension and its reversibility before the correction of valve/structural heart disease; )

- may be considered in order to adjust therapy in patients with HF who remain severely symptomatic despite initial +

IIb C
standard therapies and whose haemodynamic status is unclear.

EMB should be considered in patients with rapidly progressive HF despite standard therapy when there is a probability of a
IIa C 93

IIb C 121

Ultrasound measurement of inferior vena cava diameter may be considered for the assessment of volaemia status in patients with HF. IIb C

AHF acute heart failure; ALT alanine aminotransferase; AST aspartate aminotransferase; BNP B-type natriuretic peptide; ECG electrocardiogram; eGFR estimated
glomerular filtration rate; EMB endomyocardial biopsy; GFR glomerular filtration rate; GGTP gamma-glutamyl transpeptidase; HbA1c glycated haemoglobin; HF
heart failure; HFrEF heart failure with reduced ejection fraction; QRS Q, R, and S waves (combination of three of the graphical deflections); TIBC total iron-binding capacity;
TSAT transferrin saturation; TSH thyroid-stimulating hormone; WBC white blood cell.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.

5.10.1 Genetic testing in heart failure sufficiently high and consistent to justify routine targeted genetic
Molecular genetic analysis in patients with cardiomyopathies is re- screening. Recommendations for genetic testing in patients with
commended when the prevalence of detectable mutations is HF are based on the position statement of the European Society
Page 18 of 85 ESC Guidelines

of Cardiology Working Group on Myocardial and Pericardial Dis- hypertensive patients reduces the risk of cardiovascular disease,
eases.94 In most patients with a definite clinical diagnosis of HF, there death and hospitalization for HF.129
is no confirmatory role for routine genetic testing to establish the Recently, empaglifozin (an inhibitor of sodium-glucose cotran-
diagnosis. Genetic counselling is recommended in patients with sporter 2), has been shown to improve outcomes (including the re-
HCM, idiopathic DCM and ARVC. Restrictive cardiomyopathy duction of mortality and HF hospitalizations) in patients with type 2
and isolated non-compaction cardiomyopathies are of a possible diabetes.130 Other hypoglycaemic agents have not been shown con-
genetic origin and should also be considered for genetic testing. vincingly to reduce the risk of cardiovascular events and may in-
HCM is mostly inherited as an autosomal dominant disease with crease the risk of HF. Intensification of hypoglycaemic therapy to
variable expressivity and age-related penetrance. Currently, more drive down glycated haemoglobin (HbA1c) with agents other than
than 20 genes and 1400 mutations have been identified, most of which empagliflozin does not reduce the risk of developing HF (for details
are located in the sarcomere genes encoding cardiac b-myosin heavy see Section 11.6 on diabetes).
chain (MYH7) and cardiac myosin binding protein C (MYBPC3).88,122 Although smoking cessation has not been shown to reduce the
DCM is idiopathic in 50% of cases, about one-third of which are her- risk of developing HF, the epidemiological associations with the de-
editary. There are already more than 50 genes identified that are asso- velopment of cardiovascular disease131 suggest that such advice, if
ciated with DCM. Many genes are related to the cytoskeleton. The most followed, would be beneficial.
frequent ones are titin (TTN), lamin (LMNA) and desmin (DES).88,123 The association between alcohol intake and the risk of developing
ARVC is hereditary in most cases and is caused by gene mutations de novo HF is U-shaped, with the lowest risk with modest alcohol
that encode elements of the desmosome. Desmosomal gene muta- consumption (up to 7 drinks/week).132 134 Greater alcohol intake 7

"

tions explain 50% of cases and 10 genes are currently associated may trigger the development of toxic cardiomyopathy, and when 8

with the disease.124 present, complete abstention from alcohol is recommended.


6

"

Counselling should be performed by someone with sufficient An inverse relationship between physical activity and the risk of 

knowledge of the specific psychological, social and medical implica- HF has been reported. A recent meta-analysis found that doses 0

"

tions of a diagnosis. Determination of the genotype is important, of physical activity in excess of the guideline recommended ,

since some forms [e.g. mutations in LMNA and phospholamban minimal levels may be required for more substantial reductions in
- .

HF risk.135


(PLN)] are related to a poorer prognosis. DNA analysis could also




be of help to establish the diagnosis of rare forms, such as mitochon- It has been shown that among subjects 40 years of age with ei- 

drial cardiomyopathies. Screening of first-degree relatives for early ther cardiovascular risk factors or cardiovascular disease (but nei-
!

1 2

"

detection is recommended from early adolescence onwards, al- ther asymptomatic LV dysfunction nor overt HF), BNP-driven 4

"

though earlier screening may be considered depending on the age collaborative care between the primary care physician and the spe-
5

"

of disease onset in other family members. cialist cardiovascular centre may reduce the combined rates of LV 0

Recently, the MOGE(S) classification of inherited cardiomyopathies systolic dysfunction and overt HF.136
6

"

has been proposed, which includes the morphofunctional phenotype Statins reduce the rate of cardiovascular events and mortality; 

(M), organ(s) involvement (O), genetic inheritance pattern (G), aetio- there is also reasonable evidence that they prevent or delay the on- 

 

logical annotation (E), including genetic defect or underlying disease/ set of HF.137 140 Neither aspirin nor other antiplatelet agents, nor 

substrate, and the functional status (S) of the disease.125


!

revascularization, have been shown to reduce the risk of developing "

HF or mortality in patients with stable CAD. Obesity is also a risk


$

factor for HF,141 but the impact of treatments of obesity on the de-
 &

'

6. Delaying or preventing the velopment of HF is unknown.


&

In patients with CAD, without LV systolic dysfunction or HF, ACEIs *

development of overt heart failure


+

prevent or delay the onset of HF and reduce cardiovascular and all-


or preventing death before the cause mortality, although the benefit may be small in the
contemporary setting, especially in patients receiving aspirin.142
onset of symptoms Up-titration of reninangiotensin system antagonists and beta-blockers
There is considerable evidence that the onset of HF may be delayed to maximum tolerated dosages may improve outcomes, including HF, in
or prevented through interventions aimed at modifying risk factors patients with increased plasma concentrations of NPs.136,143
for HF or treating asymptomatic LV systolic dysfunction (see recom- A primary percutaneous coronary intervention (PCI) at the earli-
mendations table). Many trials show that control of hypertension est phase of an ST segment elevation myocardial infarction (STEMI)
will delay the onset of HF and some also show that it will prolong to reduce infarct size decreases the risk of developing a substantial
life.126 129 Different antihypertensive drugs [diuretics, ACEIs, angio- reduction in LVEF and subsequent development of HFrEF.112 Initi-
tensin receptor blockers (ARBs), beta-blockers] have been shown ation of an ACEI, a beta-blocker and an MRA immediately after a
to be effective, especially in older people, both in patients with myocardial infarction, especially when it is associated with LV
and without a history of myocardial infarction.126 128 Along with systolic dysfunction, reduces the rate of hospitalization for HF and
the ongoing discussion on optimal target blood pressure values in mortality,144 148 as do statins.137 139
hypertensive non-diabetic subjects, the recent SPRINT study has In asymptomatic patients with chronically reduced LVEF, regard-
already demonstrated that treating hypertension to a lower goal less of its aetiology, an ACEI can reduce the risk of HF requiring hos-
[systolic blood pressure (SBP) ,120 mmHg vs. ,140 mmHg] in pitalization.5,144,145 This has not yet been shown for beta-blockers
older hypertensive subjects (75 years of age) or high-risk or MRAs.
ESC Guidelines Page 19 of 85

In patients with asymptomatic LV systolic dysfunction (LVEF plantable cardioverter-defibrillator (ICD) is recommended to
,30%) of ischaemic origin who are 40 days after an AMI, an im- prolong life.149

Recommendations to prevent or delay the development of overt heart failure or prevent death before the onset of
symptoms

Recommendations Class a Level b Ref c

126, 129,
Treatment of hypertension is recommended to prevent or delay the onset of HF and prolong life. I A
150, 151

Treatment with statins is recommended in patients with or at high-risk of CAD whether or not they have LV systolic 137140,
I A
dysfunction, in order to prevent or delay the onset of HF and prolong life. 152

Counselling and treatment for smoking cessation and alcohol intake reduction is recommended for people who smoke or who
I C 131134
consume excess alcohol in order to prevent or delay the onset of HF.

130, 141,
Treating other risk factors of HF (e.g. obesity, dysglycaemia) should be considered in order to prevent or delay the onset of HF. IIa C
153155

IIa B 130 7

"

ACE-I is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction in order to 5, 144, #

I A 6

prevent or delay the onset of HF and prolong life. 145


"

ACE-I is recommended in patients with asymptomatic LV systolic dysfunction without a history of myocardial infarction, in order
I B 5
4

to prevent or delay the onset of HF.


"

ACE-I should be considered in patients with stable CAD even if they do not have LV systolic dysfunction, in order to prevent
!

- .

IIa A 142
or delay the onset of HF.
/

Beta-blocker is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction, in 

I B 146 %

order to prevent or delay the onset of HF or prolong life.


0

1 2

"

ICD is recommended in patients:


4

"

a) with asymptomatic LV systolic dysfunction (LVEF 30%) of ischaemic origin, who are at least 40 days after acute
5

"

myocardial infarction, 149,


I B
0

b) with asymptomatic non-ischaemic dilated cardiomyopathy (LVEF 30%), who receive OMT therapy, 156158 %

"

in order to prevent sudden death and prolong life.




 

ACEI angiotensin-converting enzyme inhibitor; CAD coronary artery disease; HF heart failure; ICD implantable cardioverter-defibrillator; LV left ventricular; !

LVEF left ventricular ejection fraction; OMT optimal medical therapy "

a
Class of recommendation. $

b
Level of evidence.
%

 &

c
Reference(s) supporting recommendations. '

&

7. Pharmacological treatment of Figure 7.1 shows a treatment strategy for the use of drugs (and de-
vices) in patients with HFrEF. The recommendations for each treat-
heart failure with reduced ejection ment are summarized below.
fraction Neuro-hormonal antagonists (ACEIs, MRAs and beta-blockers)
have been shown to improve survival in patients with HFrEF and
7.1 Objectives in the management of are recommended for the treatment of every patient with HFrEF,
heart failure unless contraindicated or not tolerated. A new compound
(LCZ696) that combines the moieties of an ARB (valsartan) and a
The goals of treatment in patients with HF are to improve their clin-
neprilysin (NEP) inhibitor (sacubitril) has recently been shown to
ical status, functional capacity and quality of life, prevent hospital ad-
be superior to an ACEI (enalapril) in reducing the risk of death
mission and reduce mortality. The fact that several drugs for HF
and of hospitalization for HF in a single trial with strict inclusion/ex-
have shown detrimental effects on long-term outcomes, despite
clusion criteria.162 Sacubitril/valsartan is therefore recommended to
showing beneficial effects on shorter-term surrogate markers, has
replace ACEIs in ambulatory HFrEF patients who remain symptom-
led regulatory bodies and clinical practice guidelines to seek mortal-
atic despite optimal therapy and who fit these trial criteria. ARBs
ity/morbidity data for approving/recommending therapeutic inter-
have not been consistently proven to reduce mortality in patients
ventions for HF. However, it is now recognized that preventing
with HFrEF and their use should be restricted to patients intolerant
HF hospitalization and improving functional capacity are important
of an ACEI or those who take an ACEI but are unable to tolerate an
benefits to be considered if a mortality excess is ruled out.159 161
Page 20 of 85 ESC Guidelines

MRA. Ivabradine reduces the elevated heart rate often seen in Practical guidance on how to use ACE inhibitors is given in Web
HFrEF and has also been shown to improve outcomes, and should Table 7.4.
be considered when appropriate.
The above medications should be used in conjunction with diure- 7.2.2 Beta-blockers
tics in patients with symptoms and/or signs of congestion. The use of Beta-blockers reduce mortality and morbidity in symptomatic
diuretics should be modulated according to the patients clinical patients with HFrEF, despite treatment with an ACEI and, in
status. most cases, a diuretic,167,168,170,172,173 but have not been tested
The key evidence supporting the recommendations in this in congested or decompensated patients. There is consensus
section is given in Web Table 7.1. The recommended doses of these that beta-blockers and ACEIs are complementary, and can be
disease-modifying medications are given in Table 7.2. The started together as soon as the diagnosis of HFrEF is made.
recommendations given in Sections 7.5 and 7.6 summarize drugs There is no evidence favouring the initiation of treatment
that should be avoided or used with caution in patients with HFrEF. with a beta-blocker before an ACEI has been started.176 Beta-
blockers should be initiated in clinically stable patients at a low
7.2 Treatments recommended in dose and gradually up-titrated to the maximum tolerated dose.
all symptomatic patients with heart In patients admitted due to acute HF (AHF) beta-blockers
failure with reduced ejection should be cautiously initiated in hospital, once the patient is
stabilized.
fraction
An individual patient data meta-analysis of all the major beta-
7

7.2.1 Angiotensin-converting enzyme inhibitors


"

blocker trials in HFrEF has shown no benefit on hospital admis- #

ACEIs have been shown to reduce mortality and morbidity in pa- 6

"

sions and mortality in the subgroup of patients with HFrEF who %

tients with HFrEF2,5,163 165 and are recommended unless contrain-


5

are in AF.177 However, since this is a retrospective subgroup


5

dicated or not tolerated in all symptomatic patients. ACEIs should


4

analysis, and because beta-blockers did not increase the risk,


"

be up-titrated to the maximum tolerated dose in order to achieve


the guideline committee decided not to make a separate recom-
,

adequate inhibition of the renin angiotensin aldosterone system


!

- .

mendation according to heart rhythm. Beta-blockers should be /

(RAAS). There is evidence that in clinical practice the majority of pa-




considered for rate control in patients with HFrEF and AF, es- 0

tients receive suboptimal doses of ACEI.166 ACEIs are also recom-


,

pecially in those with high heart rate (see Section 10.1 for %

mended in patients with asymptomatic LV systolic dysfunction to 1


!

details). "

reduce the risk of HF development, HF hospitalization and death


3

Beta-blockers are recommended in patients with a history of


"

(see Section 6).


5

myocardial infarction and asymptomatic LV systolic dysfunction to "

reduce the risk of death (see Section 6).


#

Pharmacological treatments indicated in patients with Practical guidance on how to use beta-blockers is given in Web 
"

symptomatic (NYHA Class II-IV) heart failure with Table 7.5. 


/

reduced ejection fraction  

7.2.3 Mineralocorticoid/aldosterone receptor antagonists !

"

a b c
Recommendations Class Level Ref MRAs (spironolactone and eplerenone) block receptors that $

bind aldosterone and, with different degrees of affinity, other ster-


%

d
An ACE-I is recommended,
 &

in addition to a beta-blocker, 2, oid hormone (e.g. corticosteroids, androgens) receptors. Spirono-


'

&

for symptomatic patients with I A 163 lactone or eplerenone are recommended in all symptomatic )

HFrEF to reduce the risk of HF 165 +

patients (despite treatment with an ACEI and a beta-blocker)


hospitalization and death.
with HFrEF and LVEF 35%, to reduce mortality and HF
A beta-blocker is recommended,
hospitalization.174,175
in addition an ACE-Id, for
167 Caution should be exercised when MRAs are used in patients
patients with stable, symptomatic I A
173
HFrEF to reduce the risk of HF with impaired renal function and in those with serum potassium
hospitalization and death. levels .5.0 mmol/L. Regular checks of serum potassium levels
An MRA is recommended for and renal function should be performed according to clinical
patients with HFrEF, who remain status.
symptomatic despite treatment
with an ACE-Id and a
I A 174, 175 Practical guidance on how to use MRAs is given in Web
beta-blocker, to reduce the risk of Table 7.6.
HF hospitalization and death.

ACEI angiotensin-converting enzyme inhibitor; HF heart failure; HFrEF 7.3 Other treatments recommended in
heart failure with reduced ejection fraction; MRA mineralocorticoid receptor
antagonist; NYHA New York Heart Association.
selected symptomatic patients with heart
a
Class of recommendation. failure with reduced ejection fraction
b
Level of evidence. 7.3.1 Diuretics
c
Reference(s) supporting recommendations.
d
Or ARB if ACEI is not tolerated/contraindicated Diuretics are recommended to reduce the signs and symptoms
of congestion in patients with HFrEF, but their effects on
ESC Guidelines Page 21 of 85

"

"

"

- .

1 2

"

"

"

"

 

"

 &

'

&

Figure 7.1 Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction. Green indicates a class I recom-
mendation; yellow indicates a class IIa recommendation. ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor blocker;
ARNI angiotensin receptor neprilysin inhibitor; BNP B-type natriuretic peptide; CRT cardiac resynchronization therapy; HF heart fail-
ure; HFrEF heart failure with reduced ejection fraction; H-ISDN hydralazine and isosorbide dinitrate; HR heart rate; ICD implantable
cardioverter defibrillator; LBBB left bundle branch block; LVAD left ventricular assist device; LVEF left ventricular ejection fraction; MR
mineralocorticoid receptor; NT-proBNP N-terminal pro-B type natriuretic peptide; NYHA New York Heart Association; OMT optimal
medical therapy; VF ventricular fibrillation; VT ventricular tachycardia. aSymptomatic NYHA Class II-IV. bHFrEF LVEF ,40%. cIf ACE
inhibitor not tolerated/contra-indicated, use ARB. dIf MR antagonist not tolerated/contra-indicated, use ARB. eWith a hospital admission for
HF within the last 6 months or with elevated natriuretic peptides (BNP . 250 pg/ml or NTproBNP . 500 pg/ml in men and 750 pg/ml in women).
f
With an elevated plasma natriuretic peptide level (BNP 150 pg/mL or plasma NT-proBNP 600 pg/mL, or if HF hospitalization within recent
12 months plasma BNP 100 pg/mL or plasma NT-proBNP 400 pg/mL). gIn doses equivalent to enalapril 10 mg b.i.d. hWith a hospital admis-
sion for HF within the previous year. iCRT is recommended if QRS 130 msec and LBBB (in sinus rhythm). jCRT should/may be considered if
QRS 130 msec with non-LBBB (in a sinus rhythm) or for patients in AF provided a strategy to ensure bi-ventricular capture in place (individua-
lized decision). For further details, see Sections 7 and 8 and corresponding web pages.
Page 22 of 85 ESC Guidelines

mortality and morbidity have not been studied in RCTs. A Co- Loop diuretics produce a more intense and shorter diuresis
chrane meta-analysis has shown that in patients with chronic HF, than thiazides, although they act synergistically and the combin-
loop and thiazide diuretics appear to reduce the risk of death ation may be used to treat resistant oedema. However, adverse
and worsening HF compared with placebo, and compared effects are more likely and these combinations should only be
with an active control, diuretics appear to improve exercise used with care. The aim of diuretic therapy is to achieve and main-
capacity.178,179 tain euvolaemia with the lowest achievable dose. The dose of the
diuretic must be adjusted according to the individual needs over
time. In selected asymptomatic euvolaemic/hypovolaemic patients,
the use of a diuretic drug might be (temporarily) discontinued. Pa-
tients can be trained to self-adjust their diuretic dose based on
Table 7.2 Evidence-based doses of disease-modifying monitoring of symptoms/signs of congestion and daily weight
drugs in key randomized trials in heart failure with measurements.
reduced ejection fraction (or after myocardial Doses of diuretics commonly used to treat HF are provided in
infarction) Table 7.3. Practical guidance on how to use diuretics is given in
Web Table 7.7.
Starting dose (mg) Target dose (mg)
ACE-I 7

Captoprila 6.25 t.i.d. 50 t.i.d.


"

Enalapril 2.5 b.i.d. 20 b.i.d.


6

"

Lisinoprilb 2.55.0 o.d. 2035 o.d.




Ramipril 2.5 o.d. 10 o.d.


"

Trandolaprila 0.5 o.d. 4 o.d. !

Table 7.3 Doses of diuretics commonly used in


- .

Beta-blockers /

patients with heart failure 0

Bisoprolol 1.25 o.d. 10 o.d.


,

Carvedilol 3.125 b.i.d. 25 b.i.d.d


1 2

Diuretics Initial dose (mg) Usual daily dose "

Metoprolol succinate (CR/XL) 12.525 o.d. 200 o.d. (mg) 4

"

Nebivololc 1.25 o.d. 10 o.d. Loop diuretics a 1

"

Furosemide 2040 40240


#

ARBs
%

Candesartan 48 o.d. 32 o.d. Bumetanide 0.51.0 15 


"

Valsartan 40 b.i.d. 160 b.i.d. Torasemide 510 1020 




 

Losartanb,c 50 o.d. 150 o.d. Thiazides b 

MRAs 2.5 2.510 "

Eplerenone 25 o.d. 50 o.d. Hydrochlorothiazide 25 12.5100 


%

&

Spironolactone 25 o.d. 50 o.d. Metolazone 2.5 2.510 (


'

&

c
ARNI lndapamide 2.5 2.55 )

Sacubitril/valsartan 49/51 b.i.d. 97/103 b.i.d. Potassium-sparing diureticsd

If -channel blocker +ACE-I/ -ACE-I/ +ACE-I/ -ACE-I/


ARB ARB ARB ARB
Ivabradine 5 b.i.d. 7.5 b.i.d.
Spironolactone/ 12.525 50 50 100
eplerenone 200
ACE angiotensin-converting enzyme; ARB angiotensin receptor blocker;
ARNI angiotensin receptor neprilysin inhibitor; b.i.d. bis in die (twice daily);
Amiloride 2.5 5 510 1020
MRA mineralocorticoid receptor antagonist; o.d. omne in die (once daily); Triamterene 25 50 100 200
t.i.d. ter in die (three times a day).
a
Indicates an ACE-I where the dosing target is derived from post-myocardial
infarction trials. ACE-I angiontensin-converting enzyme inhibitor, ARB angiotensin receptor
b
Indicates drugs where a higher dose has been shown to reduce morbidity/ blocker.
a
mortality compared with a lower dose of the same drug, but there is no substantive Oral or intravenous; dose might need to be adjusted according to volume status/
randomized, placebo-controlled trial and the optimum dose is uncertain. weight; excessive doses may cause renal impairment and ototoxicity.
b
c
Indicates a treatment not shown to reduce cardiovascular or all-cause mortality in Do not use thiazides if estimated glomerular filtration rate ,30 mL/min/1.73 m2 ,
patients with heart failure (or shown to be non-inferior to a treatment that does). except when prescribed synergistically with loop diuretics.
d c
A maximum dose of 50 mg twice daily can be administered to patients weighing lndapamide is a non-thiazide sulfonamide.
d
over 85 kg. A mineralocorticoid antagonist (MRA) i.e. spironolactone/eplerenone is always
preferred. Amiloride and triamterene should not be combined with an MRA.
ESC Guidelines Page 23 of 85

Other pharmacological treatments recommended in selected patients with symptomatic (NYHA Class II-IV) heart
failure with reduced ejection fraction

Recommendations Class a Level b Ref c


Diuretics
Diuretics are recommended in order to improve symptoms and exercise capacity in patients with signs and/or symptoms of congestion. I B 178, 179
Diuretics should be considered to reduce the risk of HF hospitalization in patients with signs and/or symptoms of congestion. IIa B 178, 179
Angiotensin receptor neprilysin inhibitor
Sacubitril/valsartan is recommended as a replacement for an ACE-I to further reduce the risk of HF hospitalization and death in
I B 162
ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRAd
I f -channel inhibitor
Ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients
with LVEF 35%, in sinus rhythm and a resting heart rate 70 bpm despite treatment with an evidence-based dose of beta- IIa B 180
blocker (or maximum tolerated dose below that), ACE-I (or ARB), and an MRA (or ARB).
Ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with
LVEF 35%, in sinus rhythm and a resting heart rate 70 bpm who are unable to tolerate or have contra-indications for a IIa C 181
beta-blocker. Patients should also receive an ACE-I (or ARB) and an MRA (or ARB). 7

"

ARB #

"

An ARB is recommended to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients unable to %

I B 182
5

tolerate an ACE-I (patients should also receive a beta-blocker and an MRA). 5

An ARB may be considered to reduce the risk of HF hospitalization and death in patients who are symptomatic despite treatment
"

-
9

IIb C
with a beta-blocker who are unable to tolerate an MRA. ,

- .

Hydralazine and isosorbide dinitrate /

35% or with an 0

LVEF <45% combined with a dilated LV in NYHA Class IIIIV despite treatment with an ACE-I a beta-blocker and an MRA IIa B 183 %

to reduce the risk of HF hospitalization and death.


1 2

"

Hydralazine and isosorbide dinitrate may be considered in symptomatic patients with HFrEF who can tolerate neither an ACE-I "

IIb B 184 0

nor an ARB (or they are contra-indicated) to reduce the risk of death. 1

"

Digoxin "

Digoxin may be considered in symptomatic patients in sinus rhythm despite treatment with an ACE-I (or ARB), a beta-blocker 

IIb B 185 

and an MRA, to reduce the risk of hospitalization (both all-cause and HF-hospitalizations).  

N-3 PUFA !

"

e
An n-3 PUFA preparation may be considered in symptomatic HF patients to reduce the risk of cardiovascular hospitalization
IIb B 186
$

and cardiovascular death. 


%

&

'

&

ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor blocker; BNP B-type natriuretic peptide; bpm beats per minute; HF heart failure; HFrEF )

heart failure with reduced ejection fraction; LVEF left ventricular ejection fraction; MRA mineralocorticoid receptor antagonist; NT-proBNP N-terminal pro-B type +

natriuretic peptide; NYHA New York Heart Association; PUFA polyunsaturated fatty acid. OMT optimal medical therapy (for HFrEF this mostly comprises an ACEI or
sacubitril/valsartan, a beta-blocker and an MRA).
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
d
Patient should have elevated natriuretic peptides (plasma BNP 150 pg/mL or plasma NT-proBNP 600 pg/mL, or if HF hospitalization within the last 12 months, plasma BNP
100 pg/mL or plasma NT-proBNP 400 pg/mL) and able to tolerate enalapril 10 mg b.i.d.
e
Applies only to preparation studied in cited trial.

7.3.2 Angiotensin receptor neprilysin inhibitor physiologic effects through binding to NP receptors and the aug-
A new therapeutic class of agents acting on the RAAS and the neu- mented generation of cGMP, thereby enhancing diuresis, natriuresis
tral endopeptidase system has been developed [angiotensin recep- and myocardial relaxation and anti-remodelling. ANP and BNP also
tor neprilysin inhibitor (ARNI)]. The first in class is LCZ696, which is inhibit renin and aldosterone secretion. Selective AT1-receptor
a molecule that combines the moieties of valsartan and sacubitril blockade reduces vasoconstriction, sodium and water retention
(neprilysin inhibitor) in a single substance. By inhibiting neprilysin, and myocardial hypertrophy.187,188
the degradation of NPs, bradykinin and other peptides is slowed. A recent trial investigated the long-term effects of sacubi-
High circulating A-type natriuretic peptide (ANP) and BNP exert tril/valsartan compared with an ACEI (enalapril) on morbidity
Page 24 of 85 ESC Guidelines

and mortality in patients with ambulatory, symptomatic HFrEF benefit 193 based on a retrospective subgroup analysis re-
with LVEF 40% (this was changed to 35% during the quested by the EMA.
study), elevated plasma NP levels (BNP 150 pg/mL or Practical guidance on how to use ivabradine is given in Web
NT-proBNP 600 pg/mL or, if they had been hospitalized Table 7.8.
for HF within the previous 12 months, BNP 100 pg/mL or
NT-proBNP 400 pg/mL), and an estimated GFR (eGFR) 7.3.4 Angiotensin II type I receptor blockers
30 mL/min/1.73 m 2 of body surface area, who were able ARBs are recommended only as an alternative in patients intolerant
to tolerate separate treatments periods with enalapril of an ACEI.182 Candesartan has been shown to reduce cardiovascu-
(10 mg b.i.d.) and sacubitril/valsartan (97/103 mg b.i.d.) during lar mortality.182 Valsartan showed an effect on hospitalization for HF
a run-in period.162 In this population, sacubitril/valsartan (97/ (but not on all-cause hospitalizations) in patients with HFrEF receiv-
103 mg b.i.d.) was superior to ACEI (enalapril 10 mg b.i.d.) in ing background ACEIs.194
reducing hospitalizations for worsening HF, cardiovascular The combination of ACEI/ARB for HFrEF was reviewed by the
mortality and overall mortality.162 Sacubitril/valsartan is there- EMA, which suggested that benefits are thought to outweigh risks
fore recommended in patients with HFrEF who fit this profile. only in a select group of patients with HFrEF in whom other treat-
Despite the superiority of sacubitril/valsartan over enalapril in ments are unsuitable. Therefore, ARBs are indicated for the treat-
the PARADIGM-HF trial, some relevant safety issues remain ment of HFrEF only in patients who cannot tolerate an ACEI
when initiating therapy with this drug in clinical practice. Symp- because of serious side effects. The combination of ACEI/ARB
tomatic hypotension was more often present in the sacubitril/ should be restricted to symptomatic HFrEF patients receiving a 7

beta-blocker who are unable to tolerate an MRA, and must be


"

valsartan group (in those 75 years of age, it affected 18% in 8

the sacubitril/valsartan group vs. 12% in the enalapril group), al- used under strict supervision. 6

"

though there was no increase in the rate of discontinuation.162 

The risk of angioedema in the trial was reduced by recruiting 7.3.5 Combination of hydralazine and isosorbide dinitrate 4

"

There is no clear evidence to suggest the use of this fixed-dose


9

only those who tolerated therapy with enalapril 10 mg b.i.d. ,

combination therapy in all patients with HFrEF. Evidence on the


!

and an sacubitril/valsartan during an active run-in phase of 5 9


- .

weeks (it resulted in a 0.4% rate of angioedema in sacubitril/val- clinical utility of this combination is scanty and comes from one /

sartan group vs. 0.2% in an enalapril group). Also, the number of relatively small RCT conducted exclusively in men and before ,

ACEIs or beta-blockers were used to treat HF.184 A subsequent


0

African American patients, who are at a higher risk of angioede-


!

1 2

"

ma, was relatively small in this study. To minimize the risk of an- RCT conducted in self-identified black patients (defined as being 3

"

of African descent) showed that addition of the combination of hy-


0

gioedema caused by overlapping ACE and neprilysin inhibition,


5

"

the ACEI should be withheld for at least 36 h before initiating dralazine and isosorbide dinitrate to conventional therapy (ACEI, 0

beta-blocker and MRA) reduced mortality and HF hospitalizations


%

sacubitril/valsartan. Combined treatment with an ACEI (or


6

in patients with HFrEF and NYHA Classes III IV.183 The results of
"

ARB) and sacubitril/valsartan is contraindicated. There are add- 

itional concerns about its effects on the degradation of this study are difficult to translate to patients of other racial or eth- 


nic origins.
 

beta-amyloid peptide in the brain, which could theoretically ac- 

celerate amyloid deposition.189 191 However, a recent small Additionally, a combination of hydralazine and isosorbide dini- !

"

14-day study with healthy subjects showed elevation of the trate may be considered in symptomatic patients with HFrEF who $

can tolerate neither ACEI nor ARB (or they are contraindicated)
%

beta-amyloid protein in the soluble rather than the aggregable


 &

form, which if confirmed over longer time periods in patients to reduce mortality. However, this recommendation is based on (
'

&

with HFrEF may indicate the cerebral safety of sacubitril/valsar- the results of the Veterans Administration Cooperative Study, )

tan.192 Long-term safety needs to be addressed. which recruited symptomatic HFrEF patients who received only di-
goxin and diuretics.184

7.3.3 If-channel inhibitor 7.4 Other treatments with less certain


Ivabradine slows the heart rate through inhibition of the I f benefits in symptomatic patients with
channel in the sinus node and therefore should only be used heart failure with reduced ejection
for patients in sinus rhythm. Ivabradine reduced the combined fraction
endpoint of mortality and hospitalization for HF in patients This section describes treatments that have shown benefits in
with symptomatic HFrEF and LVEF 35%, in sinus rhythm terms of symptomatic improvement, reduction in HF hospitaliza-
and with a heart rate 70 beats per minute (bpm) who had tions or both, and are useful additional treatments in patients
been hospitalized for HF within the previous 12 months, re- with HFrEF.
ceiving treatment with an evidence-based dose of beta-blocker
(or maximum tolerated dose), an ACEI (or ARB) and an 7.4.1 Digoxin and other digitalis glycosides
MRA. 180 The European Medicines Agency (EMA) approved Digoxin may be considered in patients in sinus rhythm with symp-
ivabradine for use in Europe in patients with HFrEF with tomatic HFrEF to reduce the risk of hospitalization (both all-cause
LVEF 35% and in sinus rhythm with a resting heart rate and HF hospitalizations),185 although its effect on top of beta-
75 bpm, because in this group ivabradine conferred a survival blockers has never been tested. The effects of digoxin in patients
ESC Guidelines Page 25 of 85

with HFrEF and AF have not been studied in RCTs, and recent stud- However, in patients who already receive a statin because of
ies have suggested potentially higher risk of events (mortality and HF underlying CAD or/and hyperlipidaemia, a continuation of this
hospitalization) in patients with AF receiving digoxin.195,196 How- therapy should be considered.
ever, this remains controversial, as another recent meta-analysis
concluded on the basis of non-RCTs that digoxin has no deleterious 7.5.2 Oral anticoagulants and antiplatelet therapy
effect on mortality in patients with AF and concomitant HF, most of Other than in patients with AF (both HFrEF and HFpEF), there is no
whom had HFrEF.197 evidence that an oral anticoagulant reduces mortality/morbidity
In patients with symptomatic HF and AF, digoxin may be use- compared with placebo or aspirin.206,207 Studies testing the non-
ful to slow a rapid ventricular rate, but it is only recommended vitamin K antagonist oral anticoagulants (NOACs) in patients with
for the treatment of patients with HFrEF and AF with rapid ven- HFrEF are currently ongoing. Patients with HFrEF receiving oral an-
tricular rate when other therapeutic options cannot be pur- ticoagulation because of concurrent AF or risk of venous thrombo-
sued. 196,198 201 Of note, the optimal ventricular rate for embolism should continue anticoagulation. Detailed information is
patients with HF and AF has not been well established, but provided in Section 10.1.
the prevailing evidence suggests that strict rate control might Similarly, there is no evidence on the benefits of antiplatelet
be deleterious. A resting ventricular rate in the range of 70 drugs (including acetylsalicylic acid) in patients with HF without ac-
90 bpm is recommended based on current opinion, although companying CAD, whereas there is a substantial risk of gastro-
one trial suggested that a resting ventricular rate of up to 110 intestinal bleeding, particularly in elderly subjects, related with
bpm might still be acceptable.202 This should be tested and re- this treatment.
7

"

fined by further research. 8

Digitalis should always be prescribed under specialist supervi-


6

"

sion. Given its distribution and clearance, caution should be ex- 7.5.3 Renin inhibitors 5

erted in females, in the elderly and in patients with reduced Aliskiren (direct renin inhibitor) failed to improve outcomes for pa- 4

"

tients hospitalized for HF at 6 months or 12 months in one study208


9

renal function. In the latter patients, digitoxin should be ,

and is not presently recommended as an alternative to an ACEI or


!

preferred.
- .

ARB.
/

7.4.2 n-3 polyunsaturated fatty acids




Treatments (or combinations of treatments) that may


!

n-3 polyunsaturated fatty acids (n-3 PUFAs) have shown a small


1 2

"

treatment effect in a large RCT.186 n-3 PUFA preparations dif- cause harm in patients with symptomatic (NYHA Class 4

"

II IV) heart failure with reduced ejection fraction


5

fer in composition and dose. Only preparations with eicosa- 1

"

pentaenoic acid (EPA) and docosahexaenoic acid (DHA) as


0

ethyl esters of at least 85% (850 mg/g) have shown an effect Recommendations Class a Level b Ref c
2

"

on the cumulative endpoint of cardiovascular death and hospi-




Thiazolidinediones (glitazones) are


/

talization. No effect of n-3 PUFA preparations containing




not recommended in patients with


III A 209, 210
 

,850 mg/g has been shown in either HFrEF or post-myocardial HF, as they increase the risk of HF 

worsening and HF hospitalization. !

infarction.203 n-3 PUFA preparations containing 850 882 mg of "

EPA and DHA as ethyl esters in the average ratio of 1 : 1.2 may NSAIDs or COX-2 inhibitors are $

not recommended in patients with 211  &

be considered as an adjunctive therapy in patients with symp- III B


HF, as they increase the risk of HF 213 '

&

tomatic HFrEF who are already receiving optimized recom-


(

worsening and HF hospitalization. )

mended therapy with an ACEI (or ARB), a beta-blocker and


*

Diltiazem or verapamil are not


an MRA. recommended in patients with
HFrEF, as they increase the III C 214
risk of HF worsening and HF
7.5 Treatments not recommended hospitalization.
(unproven benefit) in symptomatic The addition of an ARB (or renin
patients with heart failure with reduced inhibitor) to the combination
of an ACE-I and an MRA is not
ejection fraction recommended in patients with III C
7.5.1 3-Hydroxy-3-methylglutaryl-coenzyme A reductase HF, because of the increased
inhibitors (statins) risk of renal dysfunction and
hyperkalaemia.
Although statins reduce mortality and morbidity in patients with
atherosclerotic disease, statins are not effective in improving the
prognosis in patients with HFrEF. Most statin trials excluded pa- ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor
blocker; COX-2 inhibitor cyclooxygenase-2 inhibitor; HF heart failure;
tients with HF (because it was uncertain that they would bene- HFrEF heart failure with reduced ejection fraction; MRA mineralocorticoid
fit).204 The two major trials that studied the effect of statin receptor antagonist; NSAIDs non-steroidal anti-inflammatory drugs.
a
treatment in patients with chronic HF did not demonstrate any Class of recommendation.
b
Level of evidence.
evidence of benefit.205 Therefore, evidence does not support c
Reference(s) supporting recommendations
the initiation of statins in most patients with chronic HF.
Page 26 of 85 ESC Guidelines

7.6 Treatments not recommended specific guideline recommendations for other therapeutic technolo-
(believed to cause harm) in symptomatic gies, including baroreflex activation therapy,217 vagal stimulation,218
diaphragmatic pacing219,220 and cardiac contractility modula-
patients with heart failure with reduced tion;221,222 further research is required. Implantable devices to
ejection fraction monitor arrhythmias or haemodynamics are discussed elsewhere
7.6.1 Calcium-channel blockers in these guidelines.
Non-dihydropyridine calcium-channel blockers (CCBs) are not in-
dicated for the treatment of patients with HFrEF. Diltiazem and ver-
apamil have been shown to be unsafe in patients with HFrEF.214 8.1 Implantable cardioverter-defibrillator
There is a variety of dihydropyridine CCBs; some are known to A high proportion of deaths among patients with HF, especially
increase sympathetic tone and they may have a negative safety pro- those with milder symptoms, occur suddenly and unexpectedly.
file in HFrEF. There is only evidence on safety for amlodipine215 and Many of these are due to electrical disturbances, including ven-
felodipine216 in patients with HFrEF, and they can be used only if tricular arrhythmias, bradycardia and asystole, although some are
there is a compelling indication in patients with HFrEF. due to coronary, cerebral or aortic vascular events. Treatments
that improve or delay the progression of cardiovascular disease
will reduce the annual rate of sudden death, but they may have lit-
8. Non-surgical device treatment tle effect on lifetime risk and will not treat arrhythmic events when
of heart failure with reduced they occur. ICDs are effective in preventing bradycardia and cor- 7

recting potentially lethal ventricular arrhythmias. Some antiar-


ejection fraction
"

rhythmic drugs might reduce the rate of tachyarrhythmias and


#

"

This section provides recommendations on the use of ICDs and sudden death, but they do not reduce overall mortality and may 5

CRT. Currently, the evidence is considered insufficient to support increase it. 4

"

- .

Recommendations for implantable cardioverter-defibrillator in patients with heart failure /

a b c
Recommendations Class Level Ref %

1 2

Secondary prevention
"

An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients who have recovered from a I A 223226 "

ventricular arrhythmia causing haemodynamic instability, and who are expected to survive for >1 year with good functional status. 1

"

Primary prevention #

An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA 2

"

Class IIIII), and an LVEF 35% despite 3 months of OMT, provided they are expected to survive substantially longer than one
0

year with good functional status, and they have: 




 

149, 156,
IHD (unless they have had an MI in the prior 40 days see below). I A 

227 !

"

156, 157, $

DCM. I B
227
%

 &

ICD implantation is not recommended within 40 days of an MI as implantation at this time does not improve prognosis. III A 158, 228
'

&

ICD therapy is not recommended in patients in NYHA Class IV with severe symptoms refractory to pharmacological therapy *

III C 229233 +

unless they are candidates for CRT, a ventricular assist device, or cardiac transplantation.
Patients should be carefully evaluated by an experienced cardiologist before generator replacement, because management goals
IIa B 234238
and the patients needs and clinical status may have changed.
A wearable ICD may be considered for patients with HF who are at risk of sudden cardiac death for a limited period or as a
IIb C 239241
bridge to an implanted device.

CAD coronary artery disease; CRT cardiac resynchronization therapy; DCM dilated cardiomyopathy; HF heart failure; ICD implantable cardioverter-defibrillator;
IHD ischaemic heart disease; LVEF left ventricular ejection fraction; MI myocardial infarction; NYHA New York Heart Association, OMT optimal medical therapy.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.

8.1.1 Secondary prevention of sudden cardiac death survival; the decision to implant should take into account the
Compared with amiodarone treatment, ICDs reduce mortality patients view and their quality of life, the LVEF (survival bene-
in survivors of cardiac arrest and in patients who have experi- fit is uncertain when the LVEF is .35%) and the absence of
enced sustained symptomatic ventricular arrhythmias. An ICD other diseases likely to cause death within the following
is recommended in such patients when the intent is to increase year.223 225
ESC Guidelines Page 27 of 85

8.1.2 Primary prevention of sudden cardiac death ICD therapy is not recommended in patients in NYHA Class IV
Although amiodarone may have reduced mortality in older trials of with severe symptoms refractory to pharmacological therapy who
HF,242,243 contemporary studies conducted since the widespread are not candidates for CRT, a ventricular assist device or cardiac
introduction of beta-blockers suggest that it does not reduce mor- transplantation, because such patients have a very limited life ex-
tality in patients with HFrEF.227,244,245 Dronedarone246,247 and class pectancy and are likely to die from pump failure.
I antiarrhythmic agents246,248 should not be used for prevention of Patients with serious co-morbidities who are unlikely to survive
arrhythmias in this population. substantially more than 1 year are unlikely to obtain substantial
Some guideline-recommended therapies, including beta- benefit from an ICD.229 233
blockers, MRAs, sacubitril/valsartan and pacemakers with CRT Patients should be counselled as to the purpose of an ICD, com-
(CRT-Ps), reduce the risk of sudden death (see Section 7). plications related to implantation and device activation (predomin-
An ICD reduces the rate of sudden arrhythmic death in patients antly inappropriate shocks) and under what circumstances it might
with HFrEF.249,250 In patients with moderate or severe HF, a reduc- be deactivated (terminal disease) or explanted (infection, recovery
tion in sudden death may be partially or wholly offset by an increase of LV function).255
in death due to worsening HF.227 In patients with mild HF (NYHA II), If HF deteriorates, deactivation of a patients ICD may be consid-
an ICD will prevent about two deaths per year for every 100 devices ered after appropriate discussion with the patient and caregiver(s).
implanted.227 On average, patients with IHD are at greater risk of If the ICD generator reaches its end of life or requires explant-
sudden death than patients with DCM and therefore, although the ation, it should not automatically be replaced.234 238 Patients should
relative benefits are similar, the absolute benefit is greater in pa- be carefully evaluated by an experienced cardiologist before gener- 7

tients with IHD.249 Patients with longer QRS durations may also re-
"

ator replacement. Treatment goals may have changed and the risk of 8

ceive greater benefit from an ICD, but these patients should often fatal arrhythmia may be lower or the risk of non-arrhythmic death
6

"

receive a CRT device.227,251 higher. It is a matter of some controversy whether patients whose 

Two RCTs showed no benefit in patients who had an ICD im- LVEF has greatly improved and who have not required device ther- 0

"

planted within 40 days after a myocardial infarction. 158,228 Al- apy during the lifetime of the ICD should have another device im- ,

planted.234 238
!

though sudden arrhythmic deaths were reduced, this was


- .

balanced by an increase in non-arrhythmic deaths. Accordingly, Subcutaneous defibrillators may be as effective as conventional


ICDs with a lower risk from the implantation procedure.256,257


,

an ICD is contraindicated in this time period. A wearable defibril- 

lator may be considered if the patient is deemed to be at high risk They may be the preferred option for patients with difficult access
!

1 2

"

of ventricular fibrillation, although evidence from randomized or who require ICD explantation due to infection. Patients must be 4

"

trials is lacking.239 241 carefully selected, as they have limited capacity to treat serious bra-
5

"

ICD implantation is recommended only after a sufficient trial dyarrhythmia and can deliver neither antitachycardia pacing nor 0

(minimum 3 months) of optimal medical therapy (OMT) has failed CRT. Substantial RCTs with these devices and more data on safety
6

"

and efficacy are awaited.258,259


0

to increase the LVEF to .35%. However, one of the two landmark 

papers on which these recommendations are based included pa- A wearable ICD (an external defibrillator with leads and elec- 

 

tients with an LVEF .30%. Fewer than 400 patients with an LVEF trode pads attached to a wearable vest) that is able to recognize 

of 30 35% were included in the landmark studies, and although and interrupt VT/ventricular fibrillation may be considered for a lim- "

there was no statistical interaction between treatment effect and ited period of time in selected patients with HF who are at high risk
$

LVEF, the evidence of benefit is less robust in this group of patients. for sudden death but otherwise are not suitable for ICD implant-
 &

Conservative programming with long delays252 between detec-


'

ation (e.g. those with poor LVEF after acute myocardial damage until
&

tion and the ICD delivering therapy dramatically reduces the risk LV function recovers, patients scheduled for heart transplant- *

of both inappropriate (due to artefacts or AF) and appropriate ation).239 241,260 However, no prospective RCTs evaluating this de-
but unnecessary [due to self-terminating ventricular tachycardia vice have been reported.
(VT)] shocks.252 254 For detailed recommendations on the use/indications of ICD we
Patients with a QRS duration 130 ms should be considered for refer the reader to the ESC/European Heart Rhythm Association
a defibrillator with CRT (CRT-D) rather than ICD. See the guideline (EHRA) guidelines on ventricular tachyarrhythmias and sudden car-
on CRT for further details (Section 8.2). diac death.260
Page 28 of 85 ESC Guidelines

8.2 Cardiac resynchronization therapy

Recommendations for cardiac resynchronization therapy implantation in patients with heart failure

Recommendations Class a Level b Ref c


CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration 150 msec and LBBB QRS
I A 261272
morphology and with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT should be considered for symptomatic patients with HF in sinus rhythm with a QRS duration 150 msec and non-LBBB
IIa B 261272
QRS morphology and with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration of 130149 msec and LBBB QRS
I B 266, 273
morphology and with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT may be considered for symptomatic patients with HF in sinus rhythm with a QRS duration of 130149 msec and non-LBBB
IIb B 266, 273
QRS morphology and with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA class who have an indication for ventricular
I A 274277
pacing and high degree AV block in order to reduce morbidity.This includes patients with AF (see Section 10.1).
CRT should be considered for patients with LVEF 35% in NYHA Class IIIIVd despite OMT in order to improve symptoms and
275,
reduce morbidity and mortality, if they are in AF and have a QRS duration 130 msec provided a strategy to ensure bi-ventricular IIa B
278281
capture is in place or the patient is expected to return to sinus rhythm. 7

"

Patients with HFrEF who have received a conventional pacemaker or an ICD and subsequently develop worsening HF despite OMT #

IIb B 282 6

and who have a high proportion of RV pacing may be considered for upgrade to CRT.This does not apply to patients with stable HF.
"

266, 5

CRT is contra-indicated in patients with a QRS duration < 130 msec. III A 4

283285
0

"

- .

AF atrial fibrillation; AV atrio-ventricular; CRT cardiac resynchronization therapy; HF heart failure; HFrEF heart failure with reduced ejection fraction; ICD /

implantable cardioverter-defibrillator; LBBB left bundle branch block; LVEF left ventricular ejection fraction; NYHA New York Heart Association; OMT optimal medical


therapy; QRS Q, R and S waves (combination of three of the graphical deflections); RV right ventricular.
,

a %

Class of recommendation. 0

b
1 2

Level of evidence. "

c
3

Reference(s) supporting recommendations. 4

"

d
Use judgement for patients with end-stage HF who might be managed conservatively rather than with treatments to improve symptoms or prognosis.
0

"

CRT improves cardiac performance in appropriately selected pa- CRT response and was the inclusion criterion in all randomized
6

"

tients and improves symptoms286 and well-being286 and reduces


0

trials. But QRS morphology has also been related to a beneficial re- 

morbidity and mortality.266 Of the improvement in quality-adjusted




sponse to CRT. Several studies have shown that patients with left 

 

life-years (QALYs) with CRT among patients with moderate to se- bundle branch block (LBBB) morphology are more likely to respond 

vere HF, two-thirds may be attributed to improved quality of life and favourably to CRT, whereas there is less certainty about patients "

one-third to increased longevity.287 with non-LBBB morphology. However, patients with LBBB morph-
$

Only the COMPANION265 and CARE-HF trials262,263 compared


 &

ology often have wider QRS duration, and there is a current debate '

&

the effect of CRT to guideline-advised medical therapy. Most other about whether QRS duration or QRS morphology is the main pre- (

trials have compared CRT-D to ICD, and a few have compared dictor of a beneficial response to CRT. Evidence from two IPD *

CRT-P to backup pacing. The prevention of lethal bradycardia might meta-analyses indicates that after accounting for QRS duration,
be an important mechanism of benefit shared by all pacing devices. there is little evidence to suggest that QRS morphology or aetiology
In CARE-HF, at baseline, 25% of patients had a resting heart rate of of disease influence the effect of CRT on morbidity or mortal-
60 bpm.262 264 If prevention of bradycardia is important, the ef- ity.266,273 In addition, none of the landmark trials selected patients
fect of CRT will appear greater in trials where there is no device for inclusion according to QRS morphology, sex or ischaemic aeti-
in the control group. ology, nor were they powered for subgroup analyses.
Most studies of CRT have specified that the LVEF should be ,35%, The Echo-CRT283,284 trial and an IPD meta-analysis266 suggest
but RAFT267 and MADIT-CRT268,269 specified an LVEF ,30%, while possible harm from CRT when QRS duration is ,130 ms, thus im-
REVERSE270 272 specified ,40% and BLOCK-HF274 ,50%. Rela- plantation of CRT is not recommended if QRS duration is ,130
tively few patients with an LVEF of 3540% have been randomized, ms.266,283,284
but an individual participant data (IPD) meta-analysis suggests no If a patient is scheduled to receive an ICD and is in sinus rhythm
diminution of the effect of CRT in this group.266 with a QRS duration 130 ms, CRT-D should be considered if
Not all patients respond favourably to CRT.286 Several character- QRS is between 130 and 149 ms and is recommended if QRS is
istics predict improvement in morbidity and mortality, and the ex- 150 ms. However, if the primary reason for implanting a CRT
tent of reverse remodelling is one of the most important is for the relief of symptoms, then the clinician should choose
mechanisms of action of CRT. Patients with ischaemic aetiology CRT-P or CRT-D, whichever they consider appropriate. Clinical
will have less improvement in LV function due to myocardial scar tis- practice varies widely among countries. The only randomized trial
sue, which is less likely to undergo favourable remodelling.288 Con- to compare CRT-P and CRT-D265 failed to demonstrate a differ-
versely, women may be more likely to respond than men, possibly ence in morbidity or mortality between these technologies.288 If
due to smaller body and heart size.273,285,289 QRS width predicts the primary reason for implanting CRT is to improve prognosis,
ESC Guidelines Page 29 of 85

then the majority of evidence lies with CRT-D for patients in enhance contractile performance without activating extra systolic
NYHA Class II and with CRT-P for patients in NYHA Classes contractions. CCM has been evaluated in patients with HFrEF in
III IV. It is unclear whether CRT reduces the need for an ICD NYHA Classes II III with normal QRS duration (,120 ms).221,222
(by reducing the arrhythmia burden) or increases the benefit An individual patient data meta-analysis demonstrated an improve-
from an ICD (by reducing mortality rates from worsening HF, lead- ment in exercise tolerance (peak VO2) and quality of life (Minnesota
ing to longer exposure to the risk of arrhythmia). Living with Heart Failure questionnaire). Thus CCM may be consid-
When LVEF is reduced, RV pacing may exacerbate cardiac dyssyn- ered in selected patients with HF. The effect of CCM on HF morbid-
chrony. This can be prevented by CRT, which might improve patient ity and mortality remains to be established.
outcomes.274,275,277,290 However, a difference in outcome was not Most other devices under evaluation involve some modification
observed between CRT and RV pacing in a subgroup analysis of of the activity of the autonomic nervous system (ANS) by targeted
RAFT267 or in patients without HFrEF in BioPACE.291 On balance, electrical stimulation.298,299 These include vagal nerve stimulation,
CRT rather than RV pacing is recommended for patients with HFrEF spinal cord stimulation, carotid body ablation and renal denervation,
regardless of NYHA class who have an indication for ventricular pa- but so far none of the devices has improved symptoms or outcomes
cing in order to reduce morbidity, although no clear effect on mor- in RCTs.
tality was observed. Patients with HFrEF who have received a Devices for remote monitoring are discussed in Section 14.
conventional pacemaker or an ICD and subsequently develop wor-
sening HF with a high proportion of RV pacing, despite OMT, should
be considered for upgrading to CRT. 9. Treatment of heart failure with 7

"

Only two small trials have compared pharmacological therapy


preserved ejection fraction
8

alone vs. CRT in patients with AF, with conflicting results. Several
6

"

studies have indicated that CRT is superior to RV pacing in patients While there is clear agreement that the diagnosis of HFrEF requires 

undergoing atrio-ventricular (AV) node ablation.275,277,290 How-


4

an LVEF ,40%, the exact definition of HFpEF is less clear. Accord- 0

"

ever, CRT is not an indication to carry out AV node ablation except ing to the definition provided in this document (see Section 3), the ,

in rare cases when ventricular rate remains persistently high (.110 diagnosis of HFpEF requires an LVEF 50%, whereas patients with
- .

bpm) despite attempts at pharmacological rate control. A subgroup LVEF between 40 and 49% are considered to have HFmrEF (for de-


analysis of patients with AF from the RAFT study found no benefit tails, please refer to Section 3). Patients with HFmrEF have generally 

from CRT-D compared with ICD, although less than half of patients been included in trials of HFpEF. Accordingly, the guidance in this
!

1 2

"

had .90% biventricular capture.276 Observational studies report


3

section applies to patients with both HFmrEF and HFpEF. As new 4

"

that when biventricular capture is ,98%, the prognosis of patients


5

data and analyses become available, it might be possible to make re- 1

"

with CRT declines.277 Whether this association reflects a loss of re- commendations for each phenotype separately. 0

synchronization (which might be remedied by device programming), In clinical practice and clinical trials, compared with HFrEF patients,
6

"

poor placing of the LV lead (which might be avoided at implantation) only slightly fewer patients with HFpEF and HFmrEF currently appear 

to receive diuretics, beta-blockers, MRAs and ACEIs or ARBs.166,300




or greater difficulty in pacing severely diseased myocardium (which 

 

302
might not be amenable to the above) is uncertain. This observation This may reflect treatment of cardiovascular co-morbidities, such 

has not been confirmed in a randomized trial. as hypertension, CAD and AF, or extrapolation of results from trials "

Imaging tests for dyssynchrony have not yet been shown to be of conducted for these conditions showing a reduction in new-onset
$

value in selecting patients for CRT.292 Patients with extensive myo- HF,127 or failure to distinguish between guideline recommendations
 &

'

cardial scar will have less improvement in LV function with CRT, but
&

for HFrEF and HFmrEF/HFpEF or a belief that existing clinical trials (

this is true of any treatment for HFrEF and does not reliably predict provide some evidence of benefit with these agents. *

less clinical benefit.293 Pacing thresholds are higher in scarred myo- A summary of phase II and III clinical trials of patients with HFpEF
cardium and, if possible, lead placement should avoid such re- and HFmrEF is presented in Web Table 9.1.
gions.294,295 Although patients with extensive scarring have an The pathophysiology underlying HFpEF and HFmrEF is heteroge-
intrinsically worse prognosis, there is little evidence that they obtain neous, and they are associated with different phenotypes including
less prognostic benefit from CRT.266 diverse concomitant cardiovascular diseases (e.g. AF, arterial hyper-
The reader is directed to guidelines on pacing and CRT for re- tension, CAD, pulmonary hypertension) and non-cardiovascular
commendations on device implantation procedures. The value of diseases [diabetes, chronic kidney disease (CKD), anaemia, iron de-
trying to optimize AV or VV intervals after implantation using ficiency, COPD and obesity].303,304 Compared with HFrEF patients,
echo- or electrocardiographic criteria or blood pressure response hospitalizations and deaths in patients with HFmrEF/HFpEF are
is uncertain, but may be considered for patients who have had a dis- more likely to be non-cardiovascular.305,306 Therefore patients
appointing response to CRT.296,297 should be screened for cardiovascular and non-cardiovascular co-
morbidities, which if present should be managed with interventions
8.3 Other implantable electrical devices that have been shown to improve symptoms, well-being or out-
For patients with HFrEF who remain symptomatic despite OMTand do come related to that co-morbidity and not to exacerbate HF (see
not have an indication for CRT, new device therapies have been pro- Section 11).
posed and in some cases are approved for clinical use in several Euro- No treatment has yet been shown, convincingly, to reduce mor-
pean Union (EU) countries but remain under trial evaluation. bidity or mortality in patients with HFpEF or HFmrEF. However,
Cardiac contractility modulation (CCM) is similar in its mode of since these patients are often elderly and highly symptomatic, and
insertion to CRT, but it involves non-excitatory electrical stimula- often have a poor quality of life,307 an important aim of therapy
tion of the ventricle during the absolute refractory period to may be to alleviate symptoms and improve well-being.308
Page 30 of 85 ESC Guidelines

9.1 Effect of treatment on symptoms and in cardiovascular mortality.130 However, aggressive manage-
in heart failure with preserved ejection ment of dysglycaemia may be harmful.153,320
Myocardial ischaemia may contribute to symptoms, morbidity
fraction and mortality and should be considered when assessing patients.
Diuretics will usually improve congestion, if present, thereby im- However, there is only anecdotal evidence that revascularization
proving symptoms and signs of HF. The evidence that diuretics improves symptoms or outcome. Patients with angina should follow
improve symptoms is similar across the spectrum of LVEF.178,179 the same management route as patients with HFrEF.112
Evidence that beta-blockers and MRAs improve symptoms in Patients with HFpEF and HFmrEF have impaired exercise toler-
these patients is lacking. There is inconsistent evidence for an im- ance, commonly accompanied by an augmented blood pressure re-
provement in symptoms in those treated with ARBs (only for can- sponse to exercise and chronotropic incompetence. Combined
desartan was there an improvement in NYHA class)309,310 and endurance/resistance training appears safe for patients with HFpEF
ACEIs.311 and HFmrEF and improves exercise capacity (as reflected by an in-
crease in peak oxygen consumption), physical functioning score and
9.2 Effect of treatment on hospitalization diastolic function.307,321
for heart failure in heart failure with
Recommendations for treatment of patients with heart
preserved ejection fraction failure with preserved ejection fraction and heart failure
For patients in sinus rhythm, there is some evidence that nebivo- with mid-range ejection fraction 7

lol,173,312,313 digoxin, 314 spironolactone301 and candesartan310 "

might reduce HF hospitalizations. For patients in AF, beta-blockers


#

a b c
Recommendations Class Level Ref
6

"

do not appear to be effective and digoxin has not been studied. The 5

it is recommended to screen
evidence in support of either ARBs315 or ACEIs311 is inconclusive.
5

patients with HFpEF or HFmrEF


0

"

for both cardiovascular and non- ,

cardiovascular comorbidities, which,


!

9.3 Effect of treatment on mortality in


!

I C
- .

if present, should be treated provided /

heart failure with preserved ejection




safe and effective interventions exist 0

fraction to improve symptoms, well-being 

and/or prognosis. 1
!

Trials of ACEIs, ARBs, beta-blockers and MRAs have all failed to re-
"

Diuretics are recommended in 4

"

duce mortality in patients with HFpEF or HFmrEF. However, in old- congested patients with HFpEF
0

I B 178, 179
1

er patients with HFrEF, HFpEF or HFmrEF, nebivolol reduced the


"

or HFmrEF in order to alleviate 0

combined endpoint of death or cardiovascular hospitalization,173,312


#

symptoms and signs. %

with no significant interaction between treatment effect and base- 


"

line LVEF.313
/

HFmrEF heart failure with mid-range ejection fraction; HFpEF heart failure 


with preserved ejection fraction.  

a
Class of recommendation. 

9.4 Other considerations b


c
Level of evidence.
!

"

Reference(s) supporting recommendations.


#

Patients in AF should receive an anticoagulant to reduce the risk of


$

 &

thromboembolic events (for details, see the ESC guidelines of '

AF316]. Antiplatelet agents are ineffective for this purpose. Renal


&

10. Arrhythmias and conductance


)

dysfunction, which is common in this population, may contraindicate *

or increase the risk of haemorrhage with NOACs.


The optimal ventricular rate in patients with HFmrEF/HFpEF and
disturbances
AF is uncertain, and aggressive rate control might be deleterious. Ambulatory electrocardiographic monitoring can be used to investi-
Whether digoxin, beta-blockers or rate-limiting CCBs, or a combin- gate symptoms that may be due to arrhythmias,322 324 but evidence
ation of these, should be preferred is unknown. Verapamil or diltia- is lacking to support routine, systematic monitoring for all patients
zem should not be combined with a beta-blocker. There are with HF to identify tachy- and bradyarrhythmias. There is no evidence
insufficient data to recommend ablation strategies (either pulmon- that clinical decisions based on routine ambulatory electrocardio-
ary venous or AV node) for HFpEF and HFmrEF. graphic monitoring improve outcomes for patients with HF.
Circumstantial evidence suggests that treating hypertension, of- Ambulatory electrocardiographic recording detects premature
ten predominantly systolic, is important in HFmrEF/HFpEF.127,317 ventricular complexes in virtually all patients with HF. Episodes of
Diuretics, ACEIs, ARBs and MRAs all appear appropriate agents, asymptomatic, non-sustained VT are common, increasing in fre-
but beta-blockers may be less effective in reducing SBP. A recent quency with the severity of HF and ventricular dysfunction and indi-
study suggests that patients with hypertension and HFpEF or cating a poor prognosis in patients with HF, but provide little
HFmrEF should not receive an ARB (olmesartan) if they are receiv- discrimination between sudden death or death due to progressive
ing ACEIs and beta-blockers.318 HF.316,325 Bradycardia and pauses are also commonly observed, es-
The first-line oral hypoglycaemic drug for patients with HFpEF pecially at night when sympathetic activity is often lower and para-
and HFmrEF should be metformin319 (see also Section 11.6). Re- sympathetic activity higher; sleep apnoea may be a trigger.326 328
cently, a trial of empagliflozin showed a reduction in blood pressure Pauses are associated with a poor prognosis in patients with CAD
and body weight, probably by inducing glycosuria and osmotic diur- and left ventricular dysfunction.329 Bradyarrhythmias may make an
esis. Its use was associated with a reduction in hospitalization for HF important contribution to sudden death in HF.330
ESC Guidelines Page 31 of 85

10.1 Atrial fibrillation must not be given. Longer-term infusion of amiodarone should be
AF is the most common arrhythmia in HF irrespective of concomi- given only by central or long-line venous access to avoid peripheral
tant LVEF; it increases the risk of thromboembolic complications vein phlebitis. In patients with haemodynamic collapse, emergency
(particularly stroke) and may impair cardiac function, leading to electrical cardioversion is recommended (see also Section 12).
worsening symptoms of HF.316 Incident HF precipitated by AF is as-
sociated with a more benign prognosis,331 but new-onset AF in a pa- Recommendations for initial management of a
tient with established HF is associated with a worse outcome, rapid ventricular rate in patients with heart failure and
probably because it is both a marker of a sicker patient and because atrial fibrillation in the acute or chronic setting
it impairs cardiac function.332,333 Patients with chronic HF and per-
manent AF have a worse outcome than those in sinus rhythm, al- Recommendations Class a Level b Ref c
though this is largely explained by more advanced age and HF Urgent electrical cardioversion is
severity.332,333 Persistent ventricular rates .150 bpm may cause recommended if AF is thought to
HFrEF that resolves with rate control or rhythm correction (tachy- be contributing to the patients
I C
haemodynamic compromise in
cardiomyopathy).334,335 AF should be classified and managed ac-
order to improve the patient clinical
cording to the current AF guidelines (i.e. first diagnosed episode, condition.
paroxysmal, persistent, long-standing persistent or permanent), rec- For patients in NYHA Class IV, in
ognizing the uncertainty about the actual duration of the episode addition to treatment for AHF, an
and about previous undetected episodes.316 intravenous bolus of amiodarone
7

"

or, in digoxin-nave patients, an IIa B 348, 349


8

The following issues need to be considered in patients with HF #

intravenous bolus of digoxin should


6

"

presenting with AF, irrespective of LVEF, especially with a first diag- be considered to reduce the
%

nosed episode of AF or paroxysmal AF:316


5

ventricular rate. 4

"

identification of potentially correctable causes (e.g. hypothyroid- For patients in NYHA Class IIII, a ,

ism or hyperthyroidism, electrolyte disorders, uncontrolled beta-blocker, usually given orally, is -


!

safe and therefore is recommended /

hypertension, mitral valve disease) and precipitating factors I A 177


/

(e.g. recent surgery, chest infection or exacerbation of COPD/


,

ventricular rate, provided the patient 

is euvolaemic.
0

asthma, acute myocardial ischaemia, alcohol binge), as this may 1


!

"

determine management strategy;


3

For patients in NYHA Class IIII, 4

"

digoxin, should be considered


0

assessment of stroke risk and need for anticoagulation; 1


5

when ventricular rate remains highd


"

assessment of ventricular rate and need for rate control; IIa B 197 0

despite beta-blockers or when


#

evaluation of symptoms of HF and AF. beta-blockers are not tolerated or


6

"

contra-indicated.
0

For details, the reader should refer to the 2016 ESC guidelines on /

AF.316 AV node catheter ablation may be




 

considered to control heart rate 

10.1.1 Prevention of atrial fibrillation in patients with heart and relieve symptoms in patients !

"

failure unresponsive or intolerant to #

IIb B 290 $

intensive pharmacological rate and


Many treatments for HF, including ACEIs,336 ARBs,337 beta- 
%

&

rhythm control therapy, accepting


blockers177,338 and MRAs,339,340 will reduce the incidence of AF, that these patients will become (
'

&

but ivabradine may increase it.341 CRT has little effect on the inci- pacemaker dependent. )

dence of AF.342
+

Treatment with dronedarone to


Amiodarone will reduce the incidence of AF, induce pharmaco- improve ventricular rate control
III A 347
logical cardioversion, maintain more patients in sinus rhythm after is not recommended due to safety
concerns.
cardioversion and may be used to control symptoms in patients
with paroxysmal AF if beta-blockers fail to do so.343 346 Amiodar-
one should generally be restricted to short-term (,6 months) use AF atrial fibrillation; AHF acute heart failure; AV atrio-ventricular; bpm
beats per minute; HF heart failure; NYHA New York Heart Association.
in patients with paroxysmal or persistent AF to help attain sinus a
Class of recommendation.
b
rhythm and to reduce the high rate of recurrent AF immediately Level of evidence.
c
after cardioversion. Dronedarone is contraindicated in patients Reference(s) supporting recommendations.
d
The optimal ventricular rate for patients with HF and AF has not been established,
with HF and AF.246,247,347 but the prevailing evidence suggests that strict rate control might be deleterious. A
resting ventricular rate in the range of 60 100 bpm may be considered based on
10.1.2 Management of new-onset, rapid atrial fibrillation in the current opinion of this Task Force,350,351 although one trial suggested that a
patients with heart failure resting ventricular rate of up to 110 bpm might still be acceptable, and this is
If the patient has no distressing symptoms of HF, then treatment currently recommended by the ESC guidelines on AF.198,316 This should be tested
and refined by further research.
with oral beta-blockers may be initiated to provide ventricular
rate control. For patients with marked congestion who nonetheless
have few symptoms at rest, initial treatment with oral or intravenous 10.1.3 Rate control
(i.v.) digoxin is preferred. For patients in haemodynamic instability, Assessment of ventricular rate control from the radial pulse is not
an i.v. bolus of digoxin or amiodarone348,349 should be administered ideal, especially in patients with HF, as ventricular activation may
into a peripheral vein with extreme care to avoid extravasation into not always generate a palpable pulse. Rate control should be docu-
tissues; where uncertainty exists about venous access, amiodarone mented electrocardiographically. A wearable device enables
Page 32 of 85 ESC Guidelines

ventricular rate to be assessed during rest, exercise and sleep, but cardioversion.343 346 When used, the need for continued administra-
the value of routine monitoring has not yet been established. Im- tion of amiodarone should be regularly reviewed and justified.
planted devices such as pacemakers, CRT or ICDs can also be The safety and efficacy of catheter ablation in the atria and pul-
used to measure ventricular rate. monary veins (PV) as a rhythm control strategy in HF is at present
The optimal resting ventricular rate in patients with AF and HF is uncertain except for tachycardia induced cardiomyopathy.316 One
uncertain but may be between 60 100 bpm.350,352 354 One trial small study suggested that AF ablation was superior to AV node ab-
suggested that a resting ventricular rate of up to 110 bpm might still lation and CRT.360 Another study, including 203 patients with per-
be acceptable,198,202 and 2016 ESC AF guidelines recommend this sistent AF, HF and an ICD or CRT device, showed that AF ablation
threshold as the target for rate control therapy.316 However, this was superior to amiodarone in correcting AF, and this was asso-
Task Force believes that a lower rate for patients with HF may be ciated with fewer hospitalizations for HF and lower mortality.
preferable (60 100 bpm). Ventricular rates ,70 bpm are asso- Two small studies of AF ablation compared with rate control met
ciated with a worse outcome.351 This may explain why beta- with mixed success in terms of procedural complications and suc-
blockers titrated to guideline-target doses failed to reduce morbid- cess in improving symptoms.278,279 The most recent evidence
ity or mortality in patients with HFrEF and AF,177 and might also ex- from a meta-analysis that included 914 patients suggests an encour-
plain the association between digoxin and adverse outcomes aging success rate of PV ablation of AF in patients with LV dysfunc-
reported in some observational studies of AF.355 357 The optimal tion, with improvements in LVEF and functional capacity.361 These
ventricular rate during exercise is also uncertain, but may be results need to be confirmed in ongoing RCTs such as CASTLE
,110 bpm during light exercise.354 Beta-blockers, digoxin and their AF,362 AMICA and CABANA. 7

combination may be used to control ventricular rate.358 It is uncer-


"

tain which approach is optimal, but beta-blockers appear safe as the


6

"

first-line agent even if it is not clear that they reduce morbidity and Recommendations for a rhythm control management 5

mortality in patients with AF. Beta-blockers reduce ventricular rate strategy in patients with atrial fibrillation, symptomatic 4

"

heart failure (NYHA Class II IV) and left ventricular


9

during periods of activity, while digoxin exerts a greater effect at ,

systolic dysfunction and no evidence of acute


!

night.358 Persistently high ventricular rates may indicate thyrotoxi-


!

- .

cosis or excessive sympathetic activity due to congestion, which decompensation /

might respond to diuresis. Although amiodarone and non- 

dihydropyridine CCBs can reduce ventricular rate, they have Recommendations Class a Level b Ref c 1
!

"

more adverse effects and should generally be avoided in patients Electrical cardioversion or 4

"

with HFrEF and, with less certainty, in patients with HFpEF and pharmacological cardioversion with
5

"

amiodarone may be considered in


HFmrEF. Rarely, ventricular rate cannot be reduced below 100 0

patients with persisting symptoms %

110 bpm by pharmacological means alone and AV node ablation IIb B 344 6

and/or signs of HF, despite OMT and "

with ventricular pacing may be considered; in this situation, for pa- adequate control of ventricular rate,


tients with HFrEF, CRT should be considered instead of convention- to improve clinical/symptomatic 

status.
 

al RV pacing. There is little evidence, other than from registries, to 

AF ablation may be considered in


!

support a strategy of AV node ablation and CRT compared with "

order to restore sinus rhythm to


pharmacological therapy alone in patients with AF and a resting ven-
$

improve symptoms in patients with %

tricular rate ,100110 bpm (see Section 8.2).281 However, in pa-


 &

persisting symptoms and/or signs IIb B 279, 363 '

tients with a fast ventricular rate and intractable symptoms, AV node


&

of HF, despite OMT and adequate (

ablation may be considered. Also, if the patient is indicated for an control of ventricular rate, to *

improve clinical/symptomatic status.


ICD, AV node ablation with implantation of CRT-D may be a pre-
ferred option, especially if the patient has moderate to severe Amiodarone may be considered
prior to (and following) successful
symptoms. IIb B 342, 360
electrical cardioversion to maintain
10.1.4 Rhythm control sinus rhythm.
In patients with chronic HF, a rhythm control strategy (including Dronedarone is not recommended
because of an increased risk
pharmacological or electrical cardioversion) has not been shown to
of hospital admissions for
be superior to a rate control strategy in reducing mortality or morbid- III A 247, 347
cardiovascular causes and an
ity.359 Urgent cardioversion is indicated only if the AF is life threaten- increased risk of premature death in
ing, otherwise both HF and ventricular rate should be controlled NYHA Class IIIIV patients.
prior to cardioversion. A rhythm control strategy is probably best re- Class I antiarrhythmic agents are
248, 364,
served for patients with a reversible secondary cause of AF (e.g. not recommended because of an III A
365
increased risk of premature death.
hyperthyroidism) or an obvious precipitant (e.g. recent pneumonia)
and in patients with troublesome symptoms due to AF after optimiza-
tion of rate control and HF therapy. The use of class I antiarrhythmic AF atrial fibrillation; HF heart failure; NYHA New York Heart Association,
OMT optimal medical therapy.
agents and dronedarone increases morbidity and mortality in patients Patients should generally be anticoagulated for 6 weeks prior to electrical
with HF and AF and should be avoided.246,247,347 Amiodarone will cardioversion.
a
cause some patients with chronic AF to revert to sinus rhythm, Class of recommendation.
b
Level of evidence.
may reduce symptomatic paroxysms of AF and will help maintain c
Reference(s) supporting recommendations.
patients in sinus rhythm after spontaneous or electrical
ESC Guidelines Page 33 of 85

10.1.5 Thromboembolism prophylaxis HF and AF who have mechanical heart valves or at least moderate mi-
Patients with HF and AF should generally be anticoagulated and the tral stenosis, only oral vitamin K antagonists should be used for pre-
balance of benefit and risk of bleeding (using CHA2DS2-VASc and vention of thromboembolic stroke.370
HAS-BLED scores; for details, please see Web Tables 10.1 and The dabigatran dose should be reduced to 110 mg b.i.d. when cre-
10.2.) should be evaluated as recommended in the ESC guidelines atinine clearance is 30 49 mL/min, rivaroxaban to 15 mg daily and
for AF.316 A substantial proportion of patients with HF will have edoxaban to 30 mg daily when creatinine clearance is 30 50 mL/
both benefit and risk scores 3, indicating that careful consider- min and apixaban to 2.5 mg twice daily if a patient has two or
ation should be given before prescribing an oral anticoagulant and more of the following: age 80 years, serum creatinine 1.5 mg/
that regular review is subsequently needed (and correctable risk dL or body weight 60 kg.370 375 The summary of the recommen-
factors for bleeding addressed) if an oral anticoagulant is given. dations for the prevention of thromboembolism in patients with
NOACs are preferred for patients with HF with non-valvular AF, as symptomatic HF and paroxysmal or persistent/permanent AF is
NOACs compared with vitamin K antagonists seem to be at least presented in the recommendations table. For further details, please
similarly effective and even safer (less intracranial haemorrhage) in refer to the recent ESC guidelines on AF.316
patients with HF than in subjects without HF,316,366,367 although con- A left atrial occlusion device could be considered in a patient with
cerns exist about their safety in older patients with HF and poor renal AF as an alternative to an oral anticoagulant who is at high-risk both
function368,369 [for a detailed description of the interaction between of thromboembolism and of bleeding in order to avoid the risk of
NOAC and renal function, see Heidbuchel et al. 370]. In patients with haemorrhage due to anticoagulation risk.381,382
7

"

Recommendations for the prevention of thrombo-embolism in patients with symptomatic heart failure (NYHA Class II #

"

IV) and paroxysmal or persistent/permanent atrial fibrillation


%

"

Recommendations Class a Level b Ref c 9

The CHA2DS2-VASc and HAS-BLED scores are recommended tools in patients with HF for the estimation of the risk of !

I B 376, 377
- .

thromboembolism and the risk of bleeding associated with oral anticoagulation, respectively. /

An oral anticoagulant is recommended to prevent thrombo-embolism for all patients with paroxysmal or persistent/permanent
0

372375, 

AF and a CHA2DS2-VASc score 2, without contra-indications, and irrespective of whether a rate or rhythm management strategy I A %

378, 379
0

1 2

is used (including after successful cardioversion). "

NOAC treatment is contra-indicated in patients with mechanical valves or at least moderate mitral stenosis. III B 380
"

In patients with AF of 48 h duration, or when the duration of AF is unknown, an oral anticoagulant is recommended at a
"

I B 0

therapeutic dose for 3 weeks prior to electrical or pharmacological cardioversion.


#

Intravenous heparin or LMWH and TOE quided strategy is recommended for patients who have not been treated with an "

I C
0

anticoagulant dose for 3 weeks and require urgent electrical or pharmacological cardioversion for a life threatening arrhythmia. /

Combination of an oral anticoagulant and an antiplatelet agent is not recommended in patients with chronic (>12 months  

after an acute event) coronary or other arterial disease, because of a high-risk of serious bleeding. Single therapy with an oral III C 

anticoagulant is preferred after 12 months. "

For patients with HF and non-valvular AF eligible for anticoagulation based on a CHA2DS2-VASc score, NOACs rather than 
%

&

warfarin should be considered for anticoagulation as NOACs are associated with a lower risk of stroke, intracranial haemorrhage IIa B 367
and mortality, which outweigh the increased risk of gastrointestinal haemorrhage.
'

&

AF atrial fibrillation; CHA2DS2-VASc Congestive heart failure or left ventricular dysfunction, Hypertension, Age 75 (doubled), Diabetes, Stroke (doubled)-Vascular disease,
Age 65 74, Sex category (female); HAS-BLED Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio,
Elderly (.65 years), Drugs/alcohol concomitantly (1 point each); HF heart failure; LMWH low molecular weight heparin; NOAC non-vitamin K antagonist oral
anticoagulant; NYHA New York Heart Association; TOE transoesophageal echocardiography.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.

10.2 Ventricular arrhythmias revascularization for patients with HFrEF have not reduced overall
The initial management of asymptomatic ventricular arrhythmias mortality,107,385 even in subgroups of patients with angina or myo-
is correction of electrolyte abnormalities, particularly low serum cardial ischaemia,115,386 but further analysis did suggest a reduction
potassium and magnesium, withdrawal of agents that might in sudden deaths.387
provoke arrhythmias and, in patients with HFrEF, optimization Amiodarone (often in combination with a beta-blocker) may be
of pharmacological therapy with ACEIs, beta-blockers and used to suppress symptomatic ventricular arrhythmias, but it may
MRAs and sacubitril/valsartan, which all reduce the risk of sudden adversely affect prognosis, especially in patients with more severe
death.174,177,383,384 HF.227,244 Other antiarrhythmic drugs should be avoided.247 Trans-
The clinical relevance of myocardial ischaemia for the provoca- catheter radiofrequency modification of the arrhythmogenic sub-
tion of ventricular arrhythmias is uncertain, although anecdotal strate may reduce the number of appropriate ICD discharges
cases of ischaemia-induced arrhythmias exist. Randomized trials of and may be used to terminate arrhythmic storm in patients with
Page 34 of 85 ESC Guidelines

HF and frequent, recurrent ventricular tachyarrhythmias and amiodarone, digoxin and ivabradine. For patients in AF, a reduction
therefore should be considered in such patients. Seeking the in the dose of beta-blockers allowing the daytime resting ventricular
advice of the members of the HF Team with expertise in electro- rate to rise to 70 90 bpm may be considered, since evidence that
physiology is recommended in patients with recalcitrant ventricu- beta-blockers improve outcome in patients with AF is lacking.177 For
lar arrhythmias. For further details we refer the reader to the ESC/ patients with pauses but in sinus rhythm, a reduction in the dose of
EHRA guidelines on ventricular arrhythmias and sudden cardiac beta-blockers should be avoided unless the pauses are symptomatic,
death.260 prolonged or frequent, in which case the relative merits of dose re-
duction, beta-blocker withdrawal and (biventricular) pacing may be
considered. However, evidence is lacking to support a strategy of
Recommendations for the management of ventricular
pacing solely to permit initiation or titration of beta-blocker therapy
tachyarrhythmias in heart failure
in the absence of a conventional pacing indication; this strategy is not
recommended. For patients with HFrEF and high-degree AV block,
Recommendations Class a Level b Ref c
CRT is preferred over RV pacing (Section 8.2). When the cause of
Potential aggravating/precipitating bradycardia or pauses is sinus node disease with intact AV conduc-
factors (e.g. low serum potassium/
tion, then therapeutic strategies that avoid inducing ventricular dys-
magnesium, ongoing ischaemia) IIa C
should be sought and corrected in synchrony are preferred, although clinical trial evidence to support
patients with ventricular arrhythmias. this expert opinion for patients with HF is sparse. For other pacing
Treatment with beta-blocker, MRA indications, please consult the ESC Guidelines on Pacing and 7

CRT.389
"

and sacubitril/valsartan reduces 8

the risk of sudden death and is 162, 6

"

I A %

recommended for patients with 170175 5

HFrEF and ventricular arrhythmias


5

(as for other patients)(see Section 7).


Recommendations for the management of 4

"

bradyarrhythmias in heart failure


Implantation of an ICD or CRT-D
,

223226, -
!

device is recommended for selected I A


388
/

a b c


patients with HFrEF (see Section 8). Recommendations Class Level Ref


Several strategies should be




When pauses >3 seconds are %

considered to reduce
!

1 2

"

recurrent symptomatic arrhythmias bradycardia is symptomatic and the


3

"

in patients with an ICD resting ventricular rate is <50 bpm 1


0

(or in those who are not eligible IIa C in sinus rhythm or <60 bpm in AF,
"

for ICD), including attention to risk


0

it should be considered whether IIa C #

factors and optimal pharmacological


6

there is need for any rate limiting 2

"

treatment of HF, amiodarone, medications prescribed; for patients 


0

catheter ablation and CRT. in sinus rhythm beta-blockers should 




Routine use of antiarrhythmic be reduced in dose or withdrawn  

only as a last resort.




agents is not recommended in !

"

patients with HF and asymptomatic 247, 248, For patients with symptomatic, #

III A $

ventricular arrhythmias because 364, 365 prolonged or frequent pauses %

of safety concerns (worsening HF,


 &

despite adjustment of rate limiting


proarrhythmia, and death). IIb C
medication, either beta-blocker
'

&

withdrawal or pacing may be )

considered as the next step.


+

ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor


blocker; CRT cardiac resynchronization therapy; CRT-D defibrillator with Pacing solely to permit initiation or
cardiac resynchronization therapy; HF heart failure; HFrEF heart failure with titration of beta-blocker therapy in
reduced ejection fraction; ICD implantable cardioverter defibrillator; MRA III C
the absence of a conventional pacing
mineralocorticoid receptor antagonist. indication is not recommended.
a
Class of recommendation.
b
Level of evidence. In patients with HFrEF who require
c
Reference(s) supporting recommendations. pacing and who have high degree AV 274, 275,
I A
block, CRT rather than RV pacing is 290
recommended.
In patients with HFrEF who require
10.3 Symptomatic bradycardia, pauses pacing who do not have high degree
AV block, pacing modes that avoid IIa C
and atrio-ventricular block inducing or exacerbating ventricular
The ESC Guidelines on Pacing and CRT recommended intervention dyssynchrony should be considered.
when pauses exceed 6 s, even when this is not associated with symp-
toms.389 However, these recommendations were generated mainly AF atrial fibrillation; AV atrio-ventricular; bpm beats per minute; CRT
for patients without obvious myocardial dysfunction, and shorter cardiac resynchronization therapy; ECG electrocardiogram; HFrEF heart
failure with reduced ejection fraction; RV right ventricular.
pauses might require intervention in patients with HFrEF.329 If a
Class of recommendation.
b
pauses .3 s are identified on electrocardiographic monitoring, Level of evidence.
c
medications should be reviewed and the following agents stopped Reference(s) supporting recommendations.

or reduced in dose, starting with rate-limiting CCBs then


ESC Guidelines Page 35 of 85

11. Co-morbidities Table 11.1 Importance of co-morbidities in patients


with heart failure
11.1. Heart failure and co-morbidities
Co-morbidities are of great importance in HF (Table 11.1) and may 1. interfere with the diagnostic process of HF (e.g. COPD as a
affect the use of treatments for HF (e.g. it may not be possible to use potentially confounding cause of dyspnoea).390, 391
renin angiotensin system inhibitors is some patients with severe re- 2. aggravate HF symptoms and further impair quality of life.391, 392
nal dysfunction) (see Section 7). The drugs used to treat co- 3. contribute to the burden of hospitalizations and mortality,393 as the
morbidities may cause worsening of HF (e.g. NSAIDs given for arth- main cause of readmissions at 1 and 3 months.394
ritis, some anti-cancer drugs) (see Section 7). Management of co- 4. may affect the use of treatments for HF (e.g. reninangiotensin
morbidities is a key component of the holistic care of patients system inhibitors contra-indicated in some patients with severe renal
with HF (see Section 14). Many co-morbidities are actively managed dysfunction or beta-blockers relatively contra-indicated in asthma).395, 396
by specialists in the field of the co-morbidity, and these physicians 5. evidence base for HF treatment is more limited as co-morbidities were
will follow their own specialist guidelines. The current guidelines
will identify where the presence of HF should change the way a co- is therefore often lacking in the presence of co-morbidities.
morbidity would normally be treated. This may be because either 6. drugs used to treat co-morbidities may cause worsening HF (e.g.
NSAIDs given for arthritis, some anti-cancer drugs).397
safety or efficacy may be different in the presence of HF (or may sim-
ply be unknown) or because of evidence of particular effects in an 7. interaction between drugs used to treat HF and those used to treat
7

HF population, either beneficial or detrimental. HFpEF has an even "

occurrence of side effects (e.g. beta-blockers for HFrEF and beta- 8

higher prevalence of co-morbidities compared with HFrEF, and agonists for COPD and asthma).391, 395, 396
#

"

many of these may be instrumental in the progression of this


%

syndrome.398
5

HF heart failure; COPD chronic obstructive pulmonary disease; HFrEF 4

"

heart failure with reduced ejection fraction; NSAIDs non-steroidal 9

11.2 Angina and coronary artery disease anti-inflammatory drugs.


,

- .

11.2.1 Pharmacological management


/

Beta-blockers, and in selected patients ivabradine,180 are effective


0

agents for angina control, as well as an essential component of 1


0

HFrEF therapy. In HFpEF patients, they may also be used for angina significant left main stenosis and left main equivalent (proximal
"

stenosis of both the left anterior descending and left circumflex ar-
"

relief, although this has never been formally tested. In the SIGNIFY 1
0

teries) to improve prognosis.112,113 However, one needs to be


"

trial in patients with activity-limiting angina without HF, ivabradine 0

increased the risk of death from cardiovascular causes or non-fatal aware of a lack of studies including patients who have well-defined %

myocardial infarction and therefore is not recommended in this HF, therefore this recommendation is solely based on expert opin- 
"

setting.399 ion. On the basis of the results of the STICH trial [which excluded
/

Trimetazidine has been shown to exert some beneficial effect as patients with left main disease and Canadian Cardiovascular Soci-  

an add-on to beta-blockers in patients with HF and angina.400 406




ety (CCS) angina classes III IV], CABG is also recommended in pa- !

"

There are data suggesting that it may improve NYHA functional tients with HFrEF, significant CAD (left anterior descending artery #

capacity, exercise duration and LV function in patients with or multivessel disease) and LVEF 35% to reduce death and hos- 
%

&

HFrEF.402 406 Certain other effective anti-anginal drugs have pitalization for cardiovascular causes.385 Patients with .10% dys- (
'

&

been studied in sizeable numbers of HFrEF/LV dysfunction patients functional but viable LV myocardium may be more likely to benefit )

and shown to be safe [e.g. amlodipine,215,407 nicorandil408 and ni- from myocardial revascularization (and those with 10% are less
+

trates183,184,409]. The safety of other anti-anginal agents in HFrEF, likely to benefit), although this approach to patient selection for
such as ranolazine, is uncertain, while other drugs, specifically dil- revascularization is unproven. In the STICH trial, neither the pres-
tiazem and verapamil, are thought to be unsafe in patients with ence of viability nor the severity of LV remodelling identified those
HFrEF (although they may be used in HFpEF).214 Dihydropyridine who benefited from CABG in terms of a reduction in mortality.118
CCBs may all increase sympathetic tone, and their safety in For the assessment of techniques to assess myocardial viability,
HFrEF [except amlodipine215 and felodipine216] and HFpEF is please refer to Section 5. Post hoc analyses from the STICH trial
uncertain. revealed that the presence of inducible myocardial ischaemia (ei-
ther on radionuclide stress test or dobutamine stress echocardio-
11.2.2 Myocardial revascularization gram) or angina does not identify those with worse prognosis and
For indications for invasive coronary angiography in patients with greater benefit from CABG over OMT.115,386 However, CABG
HF, please refer to Section 5.8. does improve angina to a greater extent than medical therapy
Percutaneous and surgical revascularization are complementary alone.
approaches for symptomatic relief of angina in HFpEF, but whether The choice between CABG and PCI should be made by the Heart
these interventions improve outcomes is not entirely clear. Recent Team after careful evaluation of the patients clinical status and cor-
ESC guidelines on myocardial revascularization recommended onary anatomy, expected completeness of revascularization, coex-
coronary artery bypass grafting (CABG) for patients with isting valvular disease and co-morbidities.
Page 36 of 85 ESC Guidelines

Recommendations for the treatment of stable angina pectoris with symptomatic (NYHA Class II-IV) heart failure with
reduced ejection fraction112,113

Recommendations Class a Level b Ref c


Step 1

I A 167173

Step 2: on top of beta-blocker or if a beta-blocker is not tolerated


Ivabradine should be considered as an anti-anginal drug in suitable HFrEF patients (sinus rhythm and HR 70 bpm) as per 180, 410,
IIa B
recommended HFrEF management. 411
Step 3: For additional angina symptom relief except from any combination not recommended
183, 184,
A short-acting oral or transcutaneous nitrate should be considered (effective anti-anginal treatment, safe in HF). IIa A
409
A long acting oral or transcutaneous nitrate should be considered (effective anti-anginal treatment, not extensively studied in HF). IIa B 183, 184
Trimetazidine may be considered when angina persists despite treatment with a beta-blocker (or alternative) to relieve angina
IIb A 400403
(effective anti-anginal treatment, safe in HF).
7

Amlodipine may be considered in patients unable to tolerate a beta-blocker to relieve angina (effective anti-anginal treatment, safe in HF). IIb B 215, 407 "

Nicorandil may be considered in patients unable to tolerate a beta-blocker to relieve angina (effective anti-anginal treatment, 6

"

IIb C %

but safety in HF uncertain). 5

Ranolazine may be considered in patients unable to tolerate a beta-blocker to relieve angina (effective anti-anginal treatment, but 4

IIb C "

safety in HF uncertain). 9

Step 4: Myocardial revascularization -


!

385, 412,


Myocardial revascularization is recommended when angina persists despite treatment with anti-angina drugs. I A 0

413 ,

Alternatives to myocardial revascularization: combination of 3 antianginal drugs (from those listed above) may be considered 1
!

"

when angina persists despite treatment with beta-blocker, ivabradine and an extra anti-angina drug (excluding the combinations IIb C 3

"

not recommended below). 1


0

"

The following are NOT recommended: 0

(1) Combination of any of ivabradine, ranolazine, and nicorandil because of unknown safety. III C 6

"

(2) Combination of nicorandil and a nitrate (because of lack of III C 

Diltiazem and verapamil are not recommended because of their negative inotropic action and risk of worsening HF. III C 214


 

"

bpm beats per minute; HF heart failure; HFrEF heart failure with reduced ejection fraction; NYHA New York Heart Association. #

a
Class of recommendation.
$

b
%

Level of evidence.  &

c
Reference(s) supporting recommendations. (
'

&

11.3 Cachexia and sarcopenia (for frailty, resistance, reduced anabolic drive, prolonged immobilization and
please refer to Section 14) physical deconditioning, together characterized by catabolic/anabol-
ic imbalance.418 Skeletal muscle wasting, when associated with im-
Cachexia is a generalized wasting process affecting all body com-
paired mobility and symptoms (termed sarcopenia or myopenia),
partments [i.e. lean tissue (skeletal muscle), fat tissue (energy re-
occurs in 30 50% of patients with HFrEF.419 In its most severe
serves) and bone tissue (osteoporosis)]. It may occur in 515% of
form it is associated with frailty and poor morbidity and mortality.420
patients with HF, especially those with HFrEF, and more advanced
Potential treatments may include appetite stimulants, exercise
disease status.414 416 This serious complication is associated with
training120 and anabolic agents, including testosterone, in combin-
more severe symptoms and reduced functional capacity, more fre-
ation with the application of nutritional supplements and
quent hospitalization and decreased survival. Cachexia in HF can be
anti-catabolic interventions, although none is of proven benefit
diagnosed and defined as involuntary non-oedematous weight loss
and their safety is unknown.421
6% of total body weight within the previous 612 months.414 417
The causes are multifactorial, and in individual patients they are
difficult to determine. These may include pro-inflammatory immune 11.4 Cancer
activation, neurohormonal derangements, poor nutrition and mal- Certain chemotherapeutic agents can cause (or aggravate) LV sys-
absorption, impaired calorie and protein balance, anabolic hormone tolic dysfunction and HF. The best recognized of these are the
ESC Guidelines Page 37 of 85

anthracyclines (e.g. doxorubicin), trastuzumab and tyrosine kinase in depressive symptoms or improvement in cardiovascular status
inhibitors.397,422 A recent Cochrane review found that dexrazoxane compared with placebo in HFrEF patients, but this trial was not
may confer some cardioprotection in patients receiving anthracy- powered enough to prove the latter. 435 Similarly, escitalopram
clines.423 Pre- and post-evaluation of LVEF, if available with myocar- had no effect on either depression or clinical outcomes during the
dial strain imaging, is essential in patients receiving cardiotoxic 24-month follow-up as compared with placebo in patients with
chemotherapy, as detailed elsewhere.397,422 A risk score for identi- HFrEF and depression. Importantly, tricyclic antidepressants should
fying women with breast cancer at risk of developing HF during tras- be avoided, because they may cause hypotension, worsening HF and
tuzumab therapy has been developed based on age, chemotherapy arrhythmias.429,435
details, baseline cardiovascular status and other co-morbidities, and
may be helpful. 424 Chemotherapy should be discontinued and 11.6 Diabetes
HFrEF therapy commenced in patients developing moderate to se- Dysglycaemia and diabetes are very common in HF, and diabetes is
vere LV systolic dysfunction. If LV function improves, the risks and associated with poorer functional status and worse prognosis. In pa-
benefits of further chemotherapy need to be reconsid- tients with HFrEF, interventions that reduce morbidity and mortality
ered.397,425,426 Mediastinal irradiation can also lead to a variety of confer similar benefit in the presence or absence of diabetes.320 For
long-term cardiac complications. Cardiac biomarkers (NPs and tro- instance, beta-blockers improve outcome similarly, whether or not
ponins) can be used to identify patients at higher risk of cardiotoxi- the patient has diabetes, although different beta-blockers may vary
city and may be helpful in monitoring the use and dosing of in their effects on glycaemic indices.436
cardiotoxic cytotoxics.397,425,426 Whether strict glycaemic control alters the risk of cardiovascular 7

"

events in patients with HF is uncertain.437 Among patients with HF


8

who have not been treated for diabetes, higher HbA1c is associated
"

11.5 Central nervous system (including


%

with greater risk of cardiovascular events,438,439 but this may not be




depression, stroke and autonomic the case once treatment for diabetes has been commenced.439
4

"

dysfunction) In patients with diabetes and HF, glycaemic control should be im- ,

- .

Stroke and HF commonly coexist because of an overlap of shared plemented gradually and moderately, giving preference to those /

risk factors. Both contribute to a worse prognosis. Stroke may drugs, such as metformin, that have been shown to be safe and ef- 0

make self-care more difficult for the HF patient. Management of fective. In contrast to what was previously believed, metformin is


1 2

high-risk stroke patients may require balancing the risk of anticoagu- safe to use in patients with HFrEF, and it should be the treatment "

lant and antiplatelet therapies. of choice in patients with HF440,441 but is contraindicated in patients
4

"

Autonomic dysfunction is common in HFrEF, especially when se- with severe renal or hepatic impairment, because of the risk of lactic
1

"

vere.427 Combined with low blood pressure, it can make fainting and acidosis.
0

injuries more likely and can interfere with optimal dosing of beta- Insulin is required for patients with type 1 diabetes and to treat
2

"

blockers, ACEIs, ARBs and MRAs. Diuretic dosage may be reduced symptomatic hyperglycaemia in patients with type 2 diabetes and


to reduce the severity of postural hypotension. pancreatic islet b cell exhaustion. However, insulin is a powerful


 

Depression is common and is associated with worse clinical sta- sodium-retaining hormone, and when combined with a reduction 

tus and a poor prognosis in HF.428 430 It may also contribute to in glycosuria, may exacerbate fluid retention, leading to HF wor-
"

poor adherence and social isolation. A high index of suspicion is sening. Sulphonylurea derivatives have also been associated with 
%

&

needed to make the diagnosis, especially in the elderly. Routine an increased risk of worsening HF and should be used with '

&

screening using a validated questionnaire is good practice. Until caution.


(

now, the Beck Depression Inventory (BDI) and Cardiac Depression Thiazolidinediones (glitazones) cause sodium and water
*

Scale have been formally validated as reliable tools for the assess- retention and increased risk of worsening HF and hospitalization
ment of depressive mood in patients with HF,431,432 but other ques- and are not recommended in patients with HF.209,210
tionnaires have been broadly used in this group of patients (e.g. Dipeptidylpeptidase-4 inhibitors (DPP4is; gliptins), which increase
Geriatric Depression Scale, Hamilton Depression Scale, Hospital incretin secretion, thereby stimulating insulin release, and long-
Anxiety and Depression Scale). acting glucagon-like peptide 1 (GLP-1) receptor agonists, which
Psychosocial intervention and pharmacological treatment are act as incretin mimetics, improve glycaemic indices but do not re-
helpful, as well as exercise training, in patients with HFrEF and duce and may increase the risk of cardiovascular events and wor-
depression. 433 Cognitive behavioural therapy delivered in pa- sening HF.320,442,443 Importantly, there are no data on the safety of
tients with HF and major depression beyond standard care gliptins and GLP-1 analogues in patients with HF.
and a structured education programme were able to reduce Recently, empagliflozin, an inhibitor of sodium-glucose co-
depression severity, anxiety and fatigue symptoms, as well as transporter 2, reduced hospitalization for HF and mortality, but
improve social functioning and mental and HF-related quality not myocardial infarction or stroke, in patients with diabetes at
of life.434 high cardiovascular risk, some of whom had HF.130 In the absence
Selective serotonin reuptake inhibitors are thought to be safe, al- of other studies with drugs from this group, the results obtained
though the Sertraline Antidepressant Heart Attack Randomized with empaglifozin cannot be considered as a proof of a class
Trial did not confirm that sertraline provides a greater reduction effect.
Page 38 of 85 ESC Guidelines

As glycaemic derangement progresses, the judgement on gly- The management of acute hyperkalaemia (.6.0 mmol/L) may re-
caemic control should be made according to cardiac conditions, quire a short-term cessation of potassium-retaining agents and
and if the new anti-diabetic drugs are to be prescribed, they have RAAS inhibitors, but this should be minimized and RAAS inhibitors
to be closely monitored by an HF team. should be carefully reintroduced as soon as possible while monitor-
ing potassium levels. A Cochrane review452 found no trial evidence
of major outcome benefits for any emergency therapy regimen for
11.7 Erectile dysfunction
hyperkalaemia. Two new potassium binders (patiromer and sodium
Erectile dysfunction is a common and important component of qual-
zirconium cyclosilicate) are currently under consideration for regu-
ity of life in men with HF.444,445 Its treatment should include optimal
latory approval.453,454 Initial results from patients with HF are avail-
therapies for underlying cardiovascular diseases and other interfer-
able and confirm the efficacy of these therapies in reducing serum
ing co-morbidities (e.g. diabetes) and amelioration of anxiety and
potassium455 and preventing recurrent hyperkalaemia in patients
depressive symptoms. Some drugs applied for HF therapy (e.g. thia-
with HF and CKD in the context of treatment with RAAS
zide diuretics, spironolactone and beta-blockers) may augment
inhibitors.456
erectile dysfunction.444,445 Phosphodiesterase type 5 inhibitors
(PDE5Is) have been shown to have favourable haemodynamic and
anti-remodelling effects and to improve exercise capacity and qual- 11.10 Hyperlipidaemia
ity of life in patients with HFrEF,446,447 but they are contraindicated Elevated low-density lipoprotein cholesterol is uncommon in
in patients taking nitrates. HFrEF; patients with advanced HFrEF often have low concentrations 7

"

of low-density lipoprotein, which is associated with a worse progno- 8

11.8 Gout and arthritis sis. Rosuvastatin did not reduce the primary composite mortality/
6

"

Hyperuricaemia and gout are common in HF and may be caused or morbidity endpoints in two large RCTs in patients with HF with 

or without IHD, but it also did not increase risk, and may have re-
4

aggravated by diuretic treatment. Hyperuricaemia is associated with "

a worse prognosis in HFrEF.448 The current European League duced, hospitalizations.205,457 Therefore there is no evidence to rec- ,

ommend the initiation of statins in most patients with HF. However,


!

- .

Against Rheumatism (EULAR) guideline for the management of /

in patients who are already receiving a statin for CAD, a continu-




gout recommends that urate-lowering therapy (ULT) is indicated 0

in patients with recurrent acute flares, arthropathy, tophi or radio- ation of this therapy may be considered. 

1 2

graphic changes of gout, aiming to maintain a serum urate level be- "

low the saturation point for monosodium urate [,357 mmol/L "

11.11 Hypertension 0

(,6 mg/dL)].449
1

"

Hypertension is associated with an increased risk of developing HF; 0

Xanthine oxidase inhibitors (allopurinol, oxypurinol) may be used #

antihypertensive therapy markedly reduces the incidence of HF 6

to prevent gout, although their safety in HFrEF is uncertain.450 Gout


2

"

(with an exception of a-adrenoceptor blockers, which are less ef-


0

attacks are better treated with colchicine rather than with NSAIDs /

fective than other antihypertensives in preventing HF).458 A recent




(although colchicine should not be used in patients with very severe  

prospective cohort study documented that in a population with in-


renal dysfunction and may cause diarrhoea). Intra-articular corticos- 

cident HF, higher baseline systolic, diastolic and pulse pressure levels
!

teroids are an alternative for monoarticular gout, but systemic corti-


"

were associated with a higher rate of adverse events, which further $

costeroids cause sodium and water retention. %

supports the importance for optimized blood pressure control in


 &

Arthritis is a common co-morbidity and is a common cause of


this population.459 Blood pressure control is an element of the hol-
'

&

both self-taken and prescribed drugs that can worsen renal function
istic management of patients with HF.
)

and HF, especially NSAIDs. Rheumatoid arthritis is associated with


*

Negatively inotropic CCBs (i.e. diltiazem and verapamil) should


an increased risk of HFpEF. The safety of disease-modifying drugs
not be used to treat hypertension in patients with HFrEF (but are
commonly given to patients with rheumatoid arthritis has not
believed to be safe in HFpEF), and moxonidine should also be
been established in HF.
avoided in patients with HFrEF, as it increased mortality in patients
in one RCT.460 If blood pressure is not controlled with an ACEI (or
11.9 Hypokalaemia and hyperkalaemia an ARB), a beta-blocker, an MRA and a diuretic, then hydralazine
Both hypokalaemia and hyperkalaemia are associated with HF and and amlodipine215 [or felodipine216] are additional blood pressure
with many drugs used for HF treatment.451 Both can aggravate ven- lowering agents that have been shown to be safe in systolic HF. The
tricular arrhythmias. blood pressure targets recommended in hypertension guide-
Loop and thiazide diuretics reduce serum potassium, while lines 317 are applicable to HF. Uncontrolled hypertension in
ACEIs, ARBs and MRAs can all increase serum potassium. Amiloride patients with HFrEF is very rare, provided they are optimally trea-
and triamterene are sometimes used as adjunct diuretics in resistant ted for HF. In contrast, treatment of hypertension is an important
oedema and to assist in preventing hypokalaemia. The treatment of issue in patients with HFpEF. In patients with AHF, i.v. nitrates (or
hypokalaemia can involve recommending high potassium foods or sodium nitroprusside) are recommended to lower blood pressure
prescribing potassium supplements. (see Section 12).
ESC Guidelines Page 39 of 85

Recommendations for the treatment of hypertension in patients with symptomatic (NYHA Class II-IV) heart failure with
reduced ejection fraction

Recommendations Class a Level b Ref c


Step 1
2, 164,
165, 167,
168,
I A
171174,
They are also safe in HFpEF.
182,
461463
Step 2
A thiazide diuretic (or if the patient is being treated with a thiazide diuretic, switching to a loop diuretic) is recommended to
reduce blood pressure when hypertension persists despite treatment with a combination of an ACE-I (or alternatively ARB but I C
NOT together withan ACE-I), a beta-blocker and an MRA.
Step 3
Amlodipine or hydralazine is recommended to reduce blood pressure when hypertension persists despite treatment with a 183, 184,
I A
combination of an ACE-I (or alternatively ARB but NOT together withan ACE-I), a beta-blocker, an MRA and a diuretic. 215, 409 7

"

Felodipine should be considered to reduce blood pressure when hypertension persists despite treatment with a combination of
IIa B 216
#

an ACE-I (or alternatively ARB but NOT together withan ACE-I), a beta-blocker, an MRA and a diuretic. "

Moxonidine is not recommended to reduce blood pressure because of safety concerns in HFrEF patients (increased mortality). III B 460
5

"

Alpha-adrenoceptor antagonists are not recommended to reduce blood pressure because of safety concerns in HFrEF patients 458, 464,
9

III A ,

465 -
!

Diltiazem and verapamil are not recommended to reduce blood pressure in patients with HFrEF because of their negative
/

III C 214


inotropic action and risk of worsening HF. 0

1 2

"

ACE angiotensin-converting enzyme; ARB angiotensin receptor blocker; HF heart failure; HFmrEF heart failure with mid-range ejection fraction; HFpEF heart failure 3

with preserved ejection fraction; HFrEF heart failure with reduced ejection fraction; MRA mineralocorticoid receptor antagonist; NYHA New York Heart Association. "

a
5

Class of recommendation. 1

"

b
Level of evidence. 0

c
Reference(s) supporting recommendations. %

"

 

11.12 Iron deficiency and anaemia i.v. iron therapy in HFrEF patients with iron deficiency over up !

"

Iron deficiency is common in HF, as it is with other chronic ill- to 52 weeks showed reduced hospitalization rates and improved $

HF symptoms, exercise capacity and quality of life.472 Treatment


%

nesses, and it can lead to anaemia and/or skeletal muscle dysfunc-


 &

tion without anaemia.466 Within an HF population, iron deficiency with FCM may therefore result in sustainable improvement in func- (
'

&

is associated with a worse prognosis.467,468 Intravenous iron has tional capacity, symptoms and quality of life. Treatment was also
)

been specifically studied in two RCTs in patients with HF and associated with a significant reduction in hospitalizations for wor-
iron deficiency (serum ferritin ,100 mg/L or ferritin between sening HF. The number of deaths and the incidence of adverse
100 and 299 mg/L and transferrin saturation ,20%)469,470 both events were similar. Neither i.v. iron trial was powered to test
with and without anaemia. Intravenous ferric carboxymaltose for an effect on major outcomes or to evaluate separately the ef-
(FCM) has been shown to improve self-reported patient global as- fects in anaemic and non-anaemic patients. The effect of treating
sessment, quality of life and NYHA class (over 6 months) in the iron deficiency in HFpEF/HFmrEF and the long-term safety of
FAIR-HF trial469 both in anaemic and non-anaemic patients with iron therapy in either HFrEF, HFmrEF or HFpEF is unknown. The
HF, 471 and in the CONFIRM-HF trial 470 , exercise capacity im- safety of i.v. iron is unknown in patients with HF and haemoglobin
proved over 24 weeks. In the analysis of secondary endpoints in .15 g/dL.469,470 Patients with iron deficiency need to be screened
the CONFIRM-HF trial, i.v. iron reduced the risk of HF hospitaliza- for any potentially treatable/reversible causes (e.g. gastrointestinal
tions in iron-deficient patients with HFrEF.470 A meta-analysis of sources of bleeding).
Page 40 of 85 ESC Guidelines

Recommendations for the treatment of other functional status, greater risk of HF hospitalization and reduced sur-
co-morbidities in patients with heart failure vival. A diagnostic workup to seek a cause for any finding of anaemia
is indicated (e.g. occult blood loss, iron deficiency, B12/folate defi-
Recommendations Class a Level b Ref c ciency, blood dyscrasias), although in many patients no specific
cause is found. The erythropoietin-stimulating agent darbepoetin
alfa did not improve clinical outcomes in HFrEF patients with mild
Intravenous FCM should be to moderate anaemia, but led to an excess of thromboembolic
considered in symptomatic patients
events and is therefore not recommended.475
(serum ferritin <100 g/L, or
ferritin between 100299 g/L and IIa A 469, 470
transferrin saturation <20%) in
order to alleviate HF symptoms, 11.13 Kidney dysfunction (including
and improve exercise capacity and chronic kidney disease, acute kidney
quality of life.
injury, cardio-renal syndrome and
Diabetes
prostatic obstruction)
Metformin should be considered as
HF and CKD frequently coexist, share many risk factors (diabetes,
IIa C 440 ,441
control in patients with diabetes hypertension, hyperlipidaemia) and interact to worsen progno-
and HF, unless contra-indicated. sis. 476,477 CKD is generally defined as an eGFR ,60 mL/min/ 7

1.73 m 2 and/or the presence of albuminuria (high 30 300 or


"

very high .300 mg albumin/1 g of urine creatinine). Patients


6

FCM ferric carboxymaltose; HF heart failure; HFrEF heart failure with "

reduced ejection fraction.


5

a with severe renal dysfunction (eGFR ,30 mL/min/1.73m2) have 

Class of recommendation. 4

b
Level of evidence. systematically been excluded from randomized clinical trials and 0

"

c
Reference(s) supporting recommendations. therefore there is lack of evidence-based therapies in these ,

Treatments not recommended for other co-morbidities in patients with heart failure !

patients.
- .

A further deterioration in renal function, termed worsening renal




function (WRF), is used to indicate an increase in serum creatinine, 

Treatments not recommended of other co-morbidities


0

usually by .26.5 mmol/L (0.3 mg/dL) and/or a 25% increase or a


!

1 2

"

in patients with heart failure 20% drop in GFR. The importance of these apparently small changes
3

"

is that they are frequent, they promote the development and pro- 1

"

Recommendations Class a Level b Ref c gression of CKD478 and, as a consequence, can worsen the progno- 0

sis of HF. Increases in creatinine during an AHF hospitalization are


6

Sleep apnoea
2

"

Adaptive servo-ventilation is not always clinically relevant, especially when they are accompanied 

by appropriate decongestion, diuresis and haemoconcentration.479




not recommended in patients




 

with HFrEF and a predominant Large increases in serum creatinine, termed acute kidney injury
III B 473


central sleep apnoea because !

(AKI), are relatively rare in HF and are probably associated with "

of an increased all-cause and


#

the combination of diuretic therapy with other potentially nephro-


$

cardiovascular mortality. 
%

&

toxic drugs such as some antibiotics (gentamicin and trimethoprim),


Diabetes '

&

contrast media, ACEIs, ARBs, NSAIDs, etc. Of relevance, some of (

Thiazolidinediones (glitazones) are )

these drugs may accumulate if they are renally excreted. In HF, *

not recommended in patients with


+

III A 209, 210 WRF is relatively common, especially during initiation and up-
HF, as they increase the risk of HF
worsening and HF hospitalization. titration of RAAS inhibitor therapy. Despite the fact that RAAS
Arthritis blockers can frequently cause a decrease in GFR in patients with
NSAIDs or COX-2 inhibitors are HF, this reduction is usually small and should not lead to treatment
not recommended in patients with discontinuation unless there is a marked decrease, as the treatment
III B 211213
HF, as they increase the risk of HF benefit in these patients is probably largely maintained.480 When
worsening and HF hospitalization. large increases in serum creatinine occur, care should be taken to
evaluate the patient thoroughly and should include assessment of
COX-2 cyclooxygenase 2; HF heart failure; HFrEF heart failure with a possible renal artery stenosis, excessive hyper- or hypovolaemia,
reduced ejection fraction; NSAID non-steroidal anti-inflammatory drug.
a
Class of recommendation.
concomitant medication and hyperkalaemia, which frequently
b
Level of evidence. coincides with WRF.
c
Reference(s) supporting recommendations. Diuretics, especially thiazides, but also loop diuretics, may be less ef-
fective in patients with a very low GFR, and if used, should be dosed ap-
Anaemia (defined as a haemoglobin concentration ,13.0 g/dL in propriately (higher doses to achieve similar effects). Renally excreted
men and ,12.0 g/dL in women) is common in HF, particularly in drugs (e.g. digoxin, insulin and low molecular weight heparin) may accu-
hospitalized patients. It is more common in women, the elderly mulate in patients with renal impairment and may need dose adjustment
and in patients with renal impairment and is associated with ad- if renal function deteriorates. Patients with HF and coronary or periph-
vanced myocardial remodelling, inflammation and volume over- eral vascular disease are at risk of acute renal dysfunction when they
load.474 Anaemia is associated with advanced symptoms, worse undergo contrast media enhanced angiography [contrast-induced acute
ESC Guidelines Page 41 of 85

kidney injury (CI-AKI)]. Renal dysfunction and worsening renal function established that obesity is associated with lower mortality across a
is further discussed in the section about AHF (see Section 12). wide range of body mass indexes (BMIs) (see also cachexia in Section
Prostatic obstruction is common in older men and can interfere 11.3)the so-called obesity paradox also seen in other chronic ill-
with renal function; it should therefore be ruled out in men with HF nesses.414,416 Obesity should be managed as recommended in the
with deteriorating renal function. a-adrenoceptor blockers cause ESC guidelines on cardiovascular disease prevention,483 if the aim is
hypotension and sodium and water retention, and may not be to prevent future development of HF. However, these guidelines do
safe in HFrEF.458,464,465 For these reasons, 5-a-reductase inhibitors not refer to the HF patient in whom higher BMI is not adverse, and, al-
are generally preferred in the medical treatment of prostatic though often recommended for symptom benefit and risk factor con-
obstruction in patients with HF. trol, weight loss as an intervention has never been prospectively shown
to be either beneficial or safe in HFrEF. When weight loss is occurring
11.14 Lung disease (including asthma and in HF, it is associated with high mortality and morbidity, worse symp-
tom status and poor quality of life. In patients with HF with moderate
chronic obstructive pulmonary disease)
degrees of obesity (BMI ,35 kg/m2), weight loss cannot be recom-
The diagnosis of COPD and asthma may be difficult in patients with
mended. In more advanced obesity (BMI 3545 kg/m2), weight loss
HF, due to overlap in symptoms and signs, but also problems in the
may be considered to manage symptoms and exercise capacity.
interpretation of spirometry, especially in HFpEF.48,49,391 COPD
(and asthma) in patients with HF may be overdiagnosed.481 Spirom- 11.16 Sleep disturbance and
etry should be performed when patients have been stable and euvo- sleep-disordered breathing 7

laemic for at least 3 months, to avoid the confounding effect of "

Sleep-disordered breathing (SDB) occurs in more than one-third of 8

pulmonary congestion causing external obstruction of alveoli and


#

patients with HF,484 being even more prevalent in patients with


6

"

bronchioles.482 Both correctly and incorrectly labelled COPD are as-


%

AHF.485 The most common types are: central sleep apnoea (CSA, 

sociated with worse functional status and a worse prognosis in HFrEF. 4

similar to Cheyne Stokes respiration, CSR), obstructive sleep ap- 0

"

Beta-blockers are only relatively contraindicated in asthma, but 9

noea (OSA), and a mixed pattern of the two. Other causes of sleep ,

not in COPD, although a more selective b1-adrenoceptor antagon- !

disturbance include anxiety, depression, decubitus or paroxysmal


- .

ist (i.e. bisoprolol, metoprolol succinate, or nebivolol) is pre-


/

pulmonary congestion (orthopnoea and paroxysmal nocturnal dys-




ferred.48,49,391 The contraindication to beta-blockers in asthma, as


0

pnoea) and diuretic therapy causing nocturnal diuresis. Reviewing 

mentioned on pharmacy leaflets, is based on small case series pub- 0

sleep history (including asking a partner) is part of the holistic


!

1 2

"

lished in the 1980s and late 1990s with very high initial dosages in 3

care of patients with HF (see Section 14). CSA and OSA have 4

"

young patients with severe asthma. In clinical practice, starting with 0

been shown to be associated with a worse prognosis in HF.485,486


5

"

low doses of cardioselective beta-blockers combined with close


OSA is associated with an increased risk of incident HF in men.487 0

monitoring for signs of airway obstruction (wheezing, shortness of %

CSA is the most common form of SDB in HFrEF, and HFrEF is


6

breath with lengthening of the expiration) may allow the use of pro-
"

the most common cause of CSA, so they are closely linked. Screen- 

foundly effective beta-blockers in HFrEF, especially in older people 

ing for, and the diagnosis and treatment of, sleep apnoea is discussed 

where true severe asthma is uncommon. Therefore, according to


 

in detail elsewhere.484,488 Diagnosis used to require overnight poly- 

the 2015 GINA global strategy report,395,396 asthma is not an absolute !

somnography, although advanced home testing equipment which "

contraindication, but these medications should only be used under


#

can distinguish the type of sleep apnoea has been developed.


$

close medical supervision by a specialist, with consideration of the


%

 &

Nocturnal oxygen supplementation, continuous positive airway


risks for and against their use. The long-term safety of cardioactive in- '

&

pressure (CPAP), bi-level positive airway pressure (BiPAP), and adap- (

haled pulmonary drugs is uncertain and the need for their use should )

tive servo-ventilation (ASV) may be considered to treat nocturnal *

be reconsidered in patients with HFrEF, especially as their benefit in


hypoxaemia in OSA as recommended in other guidelines.489,490 An
asthma and COPD may be symptomatic only without a clear effect on
apnoea/hypopnoea index (AHI) of above 30 per hour can be treated
mortality. Oral corticosteroids can cause sodium and water reten-
using any of CPAP, BiPAP, ASV and nocturnal oxygen supplementa-
tion, potentially leading to worsening of HF, but this is not believed
tion, which have all been shown to be effective in this regard. It should
to be a problem with inhaled corticosteroids. Pulmonary hyperten-
be noted, however, that none of these interventions has been pro-
sion can complicate severe long-standing COPD, which, as a result,
spectively shown to be beneficial on major outcomes in HFrEF.
makes right-sided HF and congestion more likely. Non-invasive ven-
CPAP in HF related CSA has been shown to reduce the fre-
tilation, added to conventional therapy, improves the outcome of pa-
quency of episodes of apnoea and hypopnoea, and improve LVEF
tients with acute respiratory failure due to hypercapnic exacerbation
and 6 minute walk test distance, but did not improve prognosis or
of COPD or HF in situations of acute pulmonary oedema.
the rate of HF related hospitalizations.491
The recently published SERVE-HF473 trial has shown that ASV
11.15 Obesity used in patients with HFrEF and a predominantly CSA was neutral
Obesity is a risk factor for HF141 and complicates its diagnosis, because regarding the composite primary endpoint (all-cause death, lifesav-
it can cause dyspnoea, exercise intolerance and ankle swelling and may ing cardiovascular intervention, i.e. cardiac transplantation, implant-
result in poor-quality echocardiographic images. Obese individuals also ation of a ventricular assist device, resuscitation after sudden cardiac
have reduced NP levels.62 Obesity is more common in HFpEF than in arrest, or appropriate lifesaving shock, or unplanned hospitalization
HFrEF, although it is possible that misdiagnosis may explain at least for HF worsening), but more importantly led to an increase in both
some of this difference in prevalence. Although obesity is an independ- all-cause and cardiovascular mortality. Therefore ASV is not recom-
ent risk factor for developing HF, once HF is diagnosed, it is well mended in patients with HFrEF and predominantly CSA.
Page 42 of 85 ESC Guidelines

The safety and efficacy of alternative approaches to treating CSA Primary (organic) mitral regurgitation
in HFrEF patients, such as implantable phrenic nerve stimula- Surgery is indicated in symptomatic patients with severe organic
tion,219,220,492 are presently undergoing clinical investigation and mitral regurgitation with no contra-indications to surgery. The deci-
may require additional long term study. sion of whether to replace or repair depends mostly on valve anat-
omy, surgical expertise available, and the patients condition.
11.17. Valvular heart disease When the LVEF is , 30%, a durable surgical repair may improve
Valvular heart disease may cause or aggravate HF. This section brief- symptoms, although its effect on survival is unknown. In this situ-
ly addresses problems particularly relevant to HF, and the reader is ation, the decision to operate should take account of response to
referred to the recent guidelines on valvular disease for more medical therapy, co-morbidities, and the likelihood that the valve
information.493,494 can be repaired (rather than replaced).
Patients with HF and concomitant valvular heart disease constitute a
Secondary mitral regurgitation
high-risk population. Thus, the whole process of decision-making
This occurs because LV enlargement and remodelling lead to
through a comprehensive evaluation of the riskbenefit ratio of differ-
reduced leaflet closing. Effective medical therapy (including CRT
ent treatment strategies should be made by a multidisciplinary heart
in suitable patients) leading to reverse remodelling of the LV may
team with a particular expertise in valvular heart disease, including car-
reduce functional mitral regurgitation, and every effort should be
diologists with expertise in HF, cardiac surgeons, a structural valve
made to optimize medical treatment in these patients.
interventionist if a catheter-based therapy is being considered, imaging
Combined valve and coronary surgery should be considered in
specialists, anaesthetists and, if needed, general practitioners, geriatri- 7

symptomatic patients with LV systolic dysfunction (LVEF , 30%), "

cians, or intensive care specialists. This may be particularly beneficial 8

coronary arteries suitable for revascularization, and evidence of via- #

in patients with HF being considered for surgery, transcatheter aortic


6

"

bility. Surgery is also recommended in patients with severe mitral re-


%

valve implantation or transcatheter mitral valve intervention. 

gurgitation undergoing CABG with LVEF . 30%.


All patients should receive OMT. In those with HFrEF pharmaco-
4

"

However, a recent study in patients with moderate, secondary is- 9

logical therapy should be planned according to a previously described ,

chaemic mitral regurgitation did not prove that the addition of mitral !

algorithm (see Section 7 for details). Care must be taken using vaso-
!

- .

valve repair to CABG would lead to a higher degree of LV reverse re-


/

dilators (ACEI, ARBs, CCBs, hydralazine, and nitrates) in patients with




modelling.501 Also, there is no evidence favouring mitral valve repair 0

severe aortic stenosis in order not to cause hypotension. 

over replacement in the context of better outcomes and magnitude


%

1 2

of LV remodelling.502 In the presence of AF, atrial ablation and LA ap-


"

11.17.1. Aortic stenosis 3

"

The main concern in patients with severe aortic stenosis and re- pendage closure may be considered at the time of mitral valve surgery. 1
0

The role of isolated mitral valve surgery in patients with severe


"

duced LVEF is the entity of low-flow, low-gradient aortic stenosis 0

(valve area , 1 cm2, LVEF , 40%, mean pressure gradient , 40 functional mitral regurgitation and severe LV systolic dysfunction %

mmHg). In such individuals, low-dose dobutamine stress echocardi- (LVEF , 30%) who cannot be revascularized or have non-ischaemic 
"

cardiomyopathy is questionable, and in most patients conventional


/

ography should be considered to differentiate between patients 




with moderate aortic stenosis, and those with severe stenosis and medical and device therapy are preferred. In selected cases, repair  

low flow across the valve due to low stroke volume, and to evaluate may be considered in order to avoid or postpone transplantation. !

"

The decision should be based on comprehensive evaluation (includ-


#

for contractile or flow reserve. $

If the mean gradient is . 40 mmHg, there is theoretically no low- ing strain echocardiography or magnetic resonance imaging499,503 
%

&

er LVEF limit for aortic valve replacement in symptomatic patients and discussed within the heart team. (
'

&

with severe aortic stenosis. In patients with HF with moderate-severe, secondary mitral re- )

gurgitation who are judged inoperable or at high surgical risk, percu-


+

Transaortic valve implantation (TAVI) is recommended in pa-


tients with severe aortic stenosis who are not suitable for surgery taneous mitral valve intervention (percutaneous edge-to-edge
as assessed by a heart team and have predicted post-TAVI survival repair) may be considered in order to improve symptoms and qual-
. 1 year. TAVI should be also considered in high-risk patients with ity of life, although no RCT evidence of improvement has been pub-
severe aortic stenosis who may still be suitable for surgery, but in lished, only registry studies.504 506
whom TAVI is favoured by a heart team based on the individual 11.17.4. Tricuspid regurgitation
risk profile and anatomic suitability.495,496 In a recent trial in patients Secondary (functional) tricuspid regurgitation (TR) frequently com-
with severe aortic stenosis, TAVI with a self-expanding transcath- plicates the natural course of HF, due to annular dilatation and in-
eter aortic valve bioprosthesis was associated with a significantly creased tricuspid leaflet tethering in relation to RV pressure and/
higher rate of survival at 1 year which was sustained at 2 years.497,498 or volume overload. Severe TR causes/deteriorates symptoms
11.17.2. Aortic regurgitation and signs of right HF, thus diuretics are used to reduce peripheral
In patients with severe aortic regurgitation, aortic valve repair or re- oedema. As hepatic congestion is often present in these patients
placement is recommended in all symptomatic patients and in (additionally contributing to hyperaldosteronism), an addition of
asymptomatic patients with resting LVEF 50%, who are otherwise an MRA (in higher natriuretic doses) may improve decongestion.507
fit for surgery.499,500 Management of HF which underlies secondary TR should be opti-
mized as TR may diminish, following the treatment of its cause. In-
11.17.3. Mitral regurgitation dications for surgical correction of secondary TR complicating HF
This section refers to chronic settings while acute settings are are not clearly established.493,494 The need for correction of TR is
discussed in Section 12. usually considered at the time of surgical correction of left-sided
ESC Guidelines Page 43 of 85

Recommendations for treatment of valvular diseases in patients with heart failure

Recommendations Class a Level b Ref c


2
, LVEF <40%, mean
pressure gradient <40 mmHg), low-dose dobutamine stress echocardiography should be considered to identify those with severe IIa C
aortic stenosis suitable for valve replacement.
TAVI is recommended in patients with severe aortic stenosis who are not suitable for surgery as assessed by a heart team 495, 496,
I B
and have predicted post-TAVI survival >1 year. 509
TAVI should be considered in high-risk patients with severe aortic stenosis who may still be suitable for surgery, but in whom TAVI is
IIa A 497, 498

In patients with severe aortic regurgitation, aortic valve repair or replacement is recommended in all symptomatic patients and
I C 317
in asymptomatic patients with resting LVEF

Evidence-based medical therapy in patients with HFrEF is recommended in order to reduce functional mitral regurgitation. I C

Combined surgery of secondary mitral regurgitation and coronary artery bypass grafting should be considered in symptomatic
IIa C
patients with LV systolic dysfunction (LVEF <30%), requiring coronary revascularization for angina recalcitrant to medical therapy.
Isolated surgery of non-ischaemic regurgitant mitral valve in patients with severe functional mitral regurgitation and severe LV systolic
IIb C
dysfunction (LVEF <30%) may be considered in selected patients in order to avoid or postpone transplantation.
7

"

"

HFrEF heart failure with reduced ejection fraction; LV left ventricular; LVEF left ventricular ejection fraction; TAVI transaortic valve implantation.
%

a 

Class of recommendation. 5

b
Level of evidence.
4

"

c
Reference(s) supporting recommendations.
9

- .

493,494
valve lesions. A recent first report indicated that catheter-
0

based interventions may be possible for TR.508 Table 12.1 Factors triggering acute heart failure 1
%

"

Acute coronary syndrome.


"

12. Acute heart failure


0

"

12.1 Definition and classification Excessive rise in blood pressure.


%

"

Infection (e.g. pneumonia, infective endocarditis, sepsis).


0

AHF refers to rapid onset or worsening of symptoms and/or signs 

of HF. It is a life-threatening medical condition requiring urgent 

 

evaluation and treatment, typically leading to urgent hospital Bradyarrhythmia. 

admission. Toxic substances (alcohol, recreational drugs).


"

AHF may present as a first occurrence (de novo) or, more fre-
$

Drugs (e.g. NSAIDs, corticosteroids, negative inotropic substances, 


%

&

quently, as a consequence of acute decompensation of chronic cardiotoxic chemotherapeutics). '

&

HF, and may be caused by primary cardiac dysfunction or precipi- (

Exacerbation of chronic obstructive pulmonary disease. )

tated by extrinsic factors, often in patients with chronic HF. Acute *

Pulmonary embolism.
myocardial dysfunction (ischaemic, inflammatory or toxic), acute
valve insufficiency or pericardial tamponade are among the most Surgery and perioperative complications.
frequent acute primary cardiac causes of AHF. Decompensation Increased sympathetic drive, stress-related cardiomyopathy.
of chronic HF can occur without known precipitant factors, but Metabolic/hormonal derangements (e.g. thyroid dysfunction, diabetic
more often with one or more factors, such as infection, uncon- ketosis, adrenal dysfunction, pregnancy and peripartum related
trolled hypertension, rhythm disturbances or non-adherence with abnormalities).
drugs/diet (Table 12.1). Cerebrovascular insult.
A large number of overlapping classifications of AHF based on dif- Acute mechanical cause: myocardial rupture complicating ACS (free wall
ferent criteria have been proposed.510 513 In practice the most use- rupture, ventricular septal defect, acute mitral regurgitation), chest trauma
ful classifications are those based on clinical presentation at or cardiac intervention, acute native or prosthetic valve incompetence
secondary to endocarditis, aortic dissection or thrombosis.
admission, allowing clinicians to identify patients at high risk of com-
plications and to direct management at specific targets, which cre-
ACS acute coronary syndromes; NSAIDs non-steroidal anti-inflammatory
ates a pathway for personalized care in the AHF setting. In most drugs.
cases, patients with AHF present with either preserved (90 140
mmHg) or elevated (.140 mmHg; hypertensive AHF) systolic
blood pressure (SBP). Only 5 8% of all patients present with Another approach is to classify patients according to the presence
low SBP (i.e. ,90 mmHg; hypotensive AHF), which is associated of the following precipitants/causes leading to decompensation,
with poor prognosis, particularly when hypoperfusion is also which need to be treated/corrected urgently (see Section 12.3.1):
present.514,515 ACS, hypertensive emergency, rapid arrhythmias or severe
Page 44 of 85 ESC Guidelines

"

"

"

- .

1 2

"

"

"

"

 

"

 &

'

&

Figure 12.1 Clinical profiles of patients with acute heart failure based on the presence/absence of congestion and/or hypoperfusion
*

bradycardia/conduction disturbance, acute mechanical cause under- rales and S3 gallop; class III, with frank acute pulmonary oedema;
lying AHF or acute pulmonary embolism. class IV, cardiogenic shock, hypotension (SBP ,90 mmHg) and evi-
Clinical classification can be based on bedside physical examination dence of peripheral vasoconstriction such as oliguria, cyanosis and
in order to detect the presence of clinical symptoms/signs of conges- diaphoresis.
tion (wet vs. dry if present vs. absent) and/or peripheral hypoperfu- Definitions of the terms used in this section related to clinical
sion (cold vs. warm if present vs. absent) (Figure 12.1).514,515 The presentation of patients with AHF are provided in Table 12.2.
combination of these options identifies four groups: warm and wet
(well perfused and congested) most commonly present; cold and 12.2 Diagnosis and initial prognostic
wet (hypoperfused and congested); cold and dry (hypoperfused with- evaluation
out congestion); and warm and dry (compensated, well perfused with- The diagnostic workup needs to be started in the pre-hospital set-
out congestion). This classification may be helpful to guide therapy in ting and continued in the emergency department (ED) in order to
the initial phase and carries prognostic information.510,514,515 establish the diagnosis in a timely manner and initiate appropriate
Patients with HF complicating AMI can be classified according to management. The greater benefit of early treatment is well estab-
Killip and Kimball13 into class I, no clinical signs of HF; class II, HF with lished in ACS and now needs to be considered in the setting of
ESC Guidelines Page 45 of 85

Table 12.2 Definitions of the terms used in Section 12 on acute heart failure

Term
Symptoms/signs of congestion (left-sided) Orthopnoea, paroxysmal nocturnal dyspnoea, pulmonary rales (bilateral), peripheral oedema (bilateral).
Symptoms/signs of congestion (right-sided)
symptoms of gut congestion.
Symptoms/signs of hypoperfusion Clinical: cold sweated extremities, oliguria, mental confusion, dizziness, narrow pulse pressure.
Laboratory measures: metabolic acidosis, elevated serum lactate, elevated serum creatinine.
Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.
Hypotension Systolic BP <90 mmHg
Bradycardia Heart rate <40 bpm
Tachycardia Heart rate >120 bpm
Abnormal respiratory effort Respiratory rate >25 breaths/min with use of accessory muscles for breathing, or respiratory rate
<8 breaths/min despite dyspnoea.
Low O2 saturation O2 saturation (SaO2) <90% in pulse oximetry
Normal SaO2 neither excludes hypoxaemia (low PaO2) nor tissue hypoxia.
Hypoxaemia O2 partial pressure (PaO2) in arterial blood <80 mmHg (<10,67 kPa) (blood gas analysis).
Hypoxaemic respiratory failure (type I) PaO2 <60 mmHg (<8 kPa) 7

"

Hypercapnia CO2 partial pressure (PaCO2) in arterial blood >45 mmHg (>6 kPa) (blood gas analysis). #

"

Hypercapnic respiratory failure (type II) PaCO2 >50 mmHg (>6,65 kPa). %

Acidosis pH <7.35 4

"

Elevated blood lactate >2 mmol/L 9

Oliguria Urine output <0.5 mL/kg/h


!

- .

BP blood pressure; bpm beats per minute; PaCO2 partial pressure of carbon dioxide in arterial blood; PaO2 partial pressure of oxygen in arterial blood; SaO2 oxygen
,

saturation. 1
0

"

"

"

516,517
AHF. In parallel, coexisting life-threatening clinical conditions Chest X-ray can be a useful test for the diagnosis of AHF. Pulmon-
6

"

and/or precipitants that require urgent treatment/correction need ary venous congestion, pleural effusion, interstitial or alveolar oe- 

to be immediately identified and managed (Figure 12.2). Typically, dema and cardiomegaly are the most specific findings for AHF, 

 

an initial step in the diagnostic workup of AHF is to rule out alter- although in up to 20% of patients with AHF, chest X-ray is nearly 

normal.519 Supine chest radiographs are of limited value in AHF.


!

native causes for the patients symptoms and signs (i.e. pulmonary "

infection, severe anaemia, acute renal failure). Chest X-ray is also useful to identify alternative non-cardiac dis-
$

 &

When AHF is confirmed clinical evaluation is mandatory to select eases that may cause or contribute to the patients symptoms '

&

further management. (i.e. pneumonia, non-consolidative pulmonary infections). (

ECG is rarely normal in AHF (high negative predictive value).520 It


)

It is recommended that initial diagnosis of AHF should be based *

on a thorough history assessing symptoms, prior cardiovascular his- is also helpful in identifying underlying cardiac disease and poten-
tory and potential cardiac and non-cardiac precipitants, as well as on tial precipitants (rapid AF, acute myocardial ischaemia).
the assessment of signs/symptoms of congestion and/or hypoperfu- Immediate echocardiography is mandatory only in patients with
sion by physical examination and further confirmed by appropriate haemodynamic instability (particularly in cardiogenic shock)
additional investigations such as ECG, chest X-ray, laboratory as- and in patients suspected of acute life-threatening structural or
sessment (with specific biomarkers) and echocardiography. functional cardiac abnormalities (mechanical complications,
In patients presenting with AHF, early initiation of appropriate acute valvular regurgitation, aortic dissection). Early echocardiog-
therapy (along with relevant investigations) is of key import- raphy should be considered in all patients with de novo AHF and in
ance.516 518 those with unknown cardiac function; however, the optimal tim-
Typically, symptoms and signs of AHF reflect fluid overload (pul- ing is unknown (preferably within 48 h from admission, if the ex-
monary congestion and/or peripheral oedema) or, less often, re- pertise is available). Pocket-size echocardiography may be used
duced cardiac output with peripheral hypoperfusion (Table 12.2). as an extension of the clinical examination in the first instance
Since the sensitivity and specificity of symptoms and signs are often where available. Repeated echocardiography is usually not
not satisfactory, careful clinical evaluation needs to be followed by needed unless there is relevant deterioration in clinical status.
these additional investigations: Bedside thoracic ultrasound for signs of interstitial oedema and
Page 46 of 85 ESC Guidelines

"

"

"

- .

1 2

"

"

"

"

 

"

 &

'

&

Figure 12.2 Initial management of a patient with acute heart failure. aAcute mechanical cause: myocardial rupture complicating acute coronary
syndrome (free wall rupture, ventricular septal defect, acute mitral regurgitation), chest trauma or cardiac intervention, acute native or prosthetic
valve incompetence secondary to endocarditis, aortic dissection or thrombosis, see above.
ESC Guidelines Page 47 of 85

stimulating hormone (TSH), glucose and complete blood


Table 12.3 Causes of elevated concentrations of count; D-dimer is indicated in patients with a suspicion of
natriuretic peptides522 524 acute pulmonary embolism.
W Routine arterial blood gas is not needed and should be re-
Cardiac Heart failure
Acute coronary syndromes stricted to patients in whom oxygenation cannot be readily
Pulmonary embolism assessed by pulse oximetry. However, arterial blood gas may
Myocarditis be useful when a precise measurement of O2 and CO2 par-
Left ventricular hypertrophy
tial pressures is needed. A venous sample might acceptably
Hypertrophic or restrictive cardiomyopathy
Valvular heart disease indicate pH and CO2.
Congenital heart disease W Of note, measurement of cardiac troponins is useful for de-
Atrial and ventricular tachyarrhythmias tection of ACS as the underlying cause of AHF. However,
Heart contusion
elevated concentrations of circulating cardiac troponins
Cardioversion, ICD shock
Surgical procedures involving the heart are detected in the vast majority of patients with AHF, often
Pulmonary hypertension without obvious myocardial ischaemia or an acute coronary
Non-cardiac Advanced age event, suggesting ongoing myocyte injury or necrosis in
Ischaemic stroke these patients.525 Also in patients with acute pulmonary em-
Subarachnoid haemorrhage bolism as the underlying cause of acute decompensation,
Renal dysfunction
elevated troponins are useful for risk stratification and 7

Liver dysfunction (mainly liver cirrhosis with ascites) "

decision-making.526
8

Paraneoplastic syndrome #

W It is recommended to measure creatinine, BUN and electro-


"

Chronic obstructive pulmonary disease %

Severe infections (including pneumonia and sepsis)




lytes every 1 2 days while in the hospital and before dis- 5

Severe burns
4

charge from the hospital. Of note, more frequent testing "

Anaemia
9

Severe metabolic and hormone abnormalities might be justified according to the severity of the case. Pre- ,

- .

(e.g. thyrotoxicosis, diabetic ketosis) discharge assessment of NPs may be considered for prog- /

nostic evaluation. 0

W Assessment of procalcitonin levels may be considered in pa-




HFpEF heart failure with preserved ejection fraction; HFrEF heart failure with
%

1 2

reduced ejection fraction; ICD implantable cardioverter defibrillator. tients with AHF with suspected coexisting infection, particu- "

larly for the differential diagnosis of pneumonia and to guide


4

"

antibiotic therapy,527 if considered.


1

"

W Liver function tests are often impaired in patients with AHF


#

due to haemodynamic derangements (both reduced output


2

pleural effusion may be useful in detecting AHF if the expertise is


"

and increased venous congestion). Abnormal liver function




available. 

tests identify patients at risk of poor prognosis and may be




Laboratory tests:
 

useful for optimal management.528 530 

Natriuretic peptides.
!

W Since both hypothyroidism and hyperthyroidism may precipi-


"

Upon presentation to the ED or CCU/ICU, a plasma NP level $

tate AHF, TSH should be assessed in newly diagnosed AHF. %

(BNP, NT-proBNP or MR-proANP) should be measured in all  &

W Multiple other biomarkers, including those reflecting inflam-


patients with acute dyspnoea and suspected AHF to help in
'

&

mation, oxidative stress, neurohormonal disarray and myo-


(

the differentiation of AHF from non-cardiac causes of acute


)

cardial and matrix remodelling, have been investigated for


*

dyspnoea. NPs have high sensitivity, and normal levels in pa-


their diagnostic and prognostic value in AHF; however,
tients with suspected AHF makes the diagnosis unlikely
none has reached the stage of being recommended for rou-
(thresholds: BNP ,100 pg/mL, NT-proBNP ,300 pg/mL,
tine clinical use.
MR-proANP ,120 pg/mL).57 61,77,78,521 However, elevated
Routine invasive haemodynamic evaluation with a pulmonary ar-
levels of NPs do not automatically confirm the diagnosis of
tery catheter is not indicated for the diagnosis of AHF. It may be
AHF, as they may also be associated with a wide variety of car-
helpful in selected cases of haemodynamically unstable patients
diac and non-cardiac causes (Table 12.3). Unexpectedly low
with an unknown mechanism of deterioration. Also, routine
levels of NPs can be detected in some patients with decom-
use of an arterial line or central venous line for diagnostic pur-
pensated end-stage HF, flash pulmonary oedema or right sided
poses is not indicated.
AHF.
Other laboratory tests at presentation.
The following laboratory assessments should be performed at Numerous clinical and laboratory variables are independent pre-
admission on the blood of all patients with AHF: cardiac dictors of in-hospital complications and longer-term outcomes in
troponin, blood urea nitrogen (BUN) (or urea), creatinine, AHF syndromes, but their impact on management has not been ad-
electrolytes (sodium, potassium), liver function tests, thyroid- equately established.
Page 48 of 85 ESC Guidelines

Recommendations regarding applied diagnostic measurements

Recommendations Class a Level b Ref c


Upon presentation a measurement of plasma natriuretic peptide level (BNP, NT-proBNP or MR-proANP) is recommended in all
I A 531534
patients with acute dyspnoea and suspected AHF to help in the differentiation of AHF from non-cardiac causes of acute dyspnoea.
At admission in all patients presenting with suspected AHF, the following diagnostic tests are recommended:
a. 12-lead ECG; I C
b. chest X-ray to assess signs of pulmonary congestion and detect other cardiac or non-cardiac diseases that may
I C
cause or contribute to the patients symptoms;
c. the following laboratory assessments in the blood: cardiac troponins, BUN (or urea), creatinine, electrolytes
I C
(sodium, potassium), glucose, complete blood count, liver function tests and TSH.
Echocardiography is recommended immediately in haemodynamically unstable AHF patients and within 48 hours when
I C
cardiac structure and function are either not known or may have changed since previous studies.

AHF acute heart failure; BNP B-type natriuretic peptide; BUN blood urea nitrogen; ECG electrocardiogram; MR-proANP mid-regional pro A-type natriuretic
peptide; NT-proBNP N-terminal pro-B type natriuretic peptide; TSH thyroid-stimulating hormone
a
Class of recommendation.
b
Level of evidence. 7

c
Reference(s) supporting recommendations. "

"

12.3 Management acute pulmonary oedema. A prompt reduction in blood pressure 4

"

should be considered as a primary therapeutic target and initiated


9

AHF is a life-threatening medical condition, thus rapid transfer to the ,

as soon as possible. Aggressive blood pressure reduction (in the


!

nearest hospital should be pursued, preferably to a site with a cardiology


- .

range of 25% during the first few hours and cautiously thereafter)
/

department and/or a coronary care/intensive care unit (CCU/ICU).




with i.v. vasodilators in combination with loop diuretics is


0

Early diagnosis is important in AHF. Therefore, all patients with 

recommended.317,536,537
%

suspected AHF should have a diagnostic workup and appropriate


!

1 2

"

pharmacological and non-pharmacological treatment should be Rapid arrhythmias or severe bradycardia/conduction dis- 3

"

turbance. Severe rhythm disturbances in patients with AHF and


0

started promptly and in parallel.


5

"

Initial evaluation and continued non-invasive monitoring of the unstable conditions should be corrected urgently with medical 0

therapy, electrical cardioversion or temporary pacing260,316,389


%

patients vital cardiorespiratory functions, including pulse oximetry,


6

(see also Section 10.1 for AF management).


"

blood pressure, respiratory rate and a continuous ECG instituted 

within minutes, is essential to evaluate whether ventilation, periph- Electrical cardioversion is recommended if an atrial or ven- 


tricular arrhythmia is thought to be contributing to the patients


 

eral perfusion, oxygenation, heart rate and blood pressure are ad- 

equate. Urine output should also be monitored, although routine haemodynamic compromise in order to restore sinus rhythm and !

"

urinary catheterization is not recommended. improve the patients clinical condition. $

Patients with AHF and incessant ventricular arrhythmias pre-


%

Patients with respiratory distress/failure or haemodynamic com-


 &

promise should be triaged to a location where immediate respira- sent a challenging scenario, as arrhythmias and haemodynamic (
'

&

tory and cardiovascular support can be provided (Figure 12.2). instability operate in a vicious circle, perpetuating each other. In )

selected cases, immediate angiography (with resultant revascular-


ization, if needed) and electrophysiological testing with radiofre-
12.3.1 Identification of precipitants/causes leading to quency ablation may be considered.260
decompensation that needs urgent management Acute mechanical cause underlying AHF. This may present
The next step should comprise the identification of major precipitants/ as a mechanical complication of ACS (free wall rupture, ventricu-
causes leading to decompensation, which should be managed urgently lar septal defect, acute mitral regurgitation), chest trauma or car-
to avoid further deterioration (Figure 12.2). These include the following: diac intervention, or as acute native or prosthetic valve
Acute coronary syndrome. Patients presenting with ACS incompetence secondary to endocarditis, aortic dissection or
thrombosis and comprise rare causes of obstruction (e.g. cardiac
should be managed according to the ESC guidelines on non-ST
tumours). Echocardiography is essential for diagnosis, and treat-
elevation ACS (NSTE-ACS) and STEMI.114,535 Coexistence of
these two clinical conditions (ACS and AHF) always identifies a ment typically requires circulatory support with surgical or per-
cutaneous intervention.
very-high-risk group where an immediate (i.e. ,2 h from hospital
Acute pulmonary embolism. When acute pulmonary em-
admission in patients with NSTEMI, analogous to STEMI manage-
ment) invasive strategy with intent to perform revascularization is bolism is confirmed as the cause of shock or hypotension, im-
mediate specific treatment is recommended with primary
recommended, irrespective of ECG or biomarker findings.114,535
reperfusion either with thrombolysis, catheter-based approach
See below for patients presenting with persistent haemodynamic
instability due to mechanical ACS complication. or surgical embolectomy.526 Patients presenting with acute pul-
monary embolism should be managed according to the appro-
Hypertensive emergency. AHF precipitated by rapid and ex-
priate guidelines.526
cessive increase in arterial blood pressure typically manifests as
ESC Guidelines Page 49 of 85

Identification of acute aetiologies/precipitants with subsequent signs/symptoms of hypoperfusion


initiation of specific treatments should be done within the immedi- oxygen saturation (SpO2) ,90% (despite supplemental oxygen)
ate phase of AHF management (initial 60 120 min) (Figure 12.2). use of accessory muscles for breathing, respiratory rate
.25/min
12.3.2 Criteria for hospitalization in ward vs. intensive
care/coronary care unit heart rate ,40 or .130 bpm, SBP ,90 mmHg.540
The remaining patients with AHF usually need hospitalization on
Patients with persistent, significant dyspnoea or haemodynamic an ordinary ward. Only a few patients admitted to the ED with
instability should be triaged to a location where immediate resus- AHF (mainly as exacerbation of HF symptoms with subtle signs
citative support can be provided if needed. of congestion) after a small dose of diuretics and some adjust-
For high-risk patients (i.e. with persistent, significant dyspnoea, ments of oral therapy can be discharged directly home from
haemodynamic instability, recurrent arrhythmias, AHF and associated the ED with advice to be clinically followed in an outpatient clinic.
ACS), initial care should be provided in a high-dependency setting Step-down care from the ICU/CCU is dictated by clinical stabil-
(ICU/CCU). Clinical risk algorithms developed to predict in-hospital ization and resolution of morbid conditions. Further treatment
mortality of patients with AHF can assist in determining which patients will be continued with the involvement of a multidisciplinary
in the ED need the highest level of inpatient care.538,539 team and discharge planning.
The criteria for ICU/CCU admission include any of the following: 12.3.3 Management of the early phase
need for intubation (or already intubated) Oxygen therapy and/or ventilatory support 7

"

Recommendations for the management of patients with acute heart failure: oxygen therapy and ventilatory support "

a b c
Recommendations Class Level Ref 0

"

Monitoring of transcutaneous arterial oxygen saturation (SpO2) is recommended. I C ,

- .

Measurement of blood pH and carbon dioxide tension (possibly including lactate) should be considered, especially in /

patients with acute pulmonary oedema or previous history of COPD using venous blood. In patients with cardiogenic IIa C


shock arterial blood is preferable. ,

Oxygen therapy is recommended in patients with AHF and SpO2 <90% or PaO2 <60 mmHg (8.0 kPa) to correct hypoxaemia. I C 1
!

"

Non-invasive positive pressure ventilation (CPAP, BiPAP) should be considered in patients with respiratory distress 4

"

(respiratory rate >25 breaths/min, SpO 2 <90%) and started as soon as possible in order to decrease respiratory distress
0

"

and reduce the rate of mechanical endotracheal intubation. IIa B 541545 0

Non-invasive positive pressure ventilation can reduce blood pressure and should be used with caution in hypotensive
#

patients. Blood pressure should be monitored regularly when this treatment is used.
2

"

Intubation is recommended, if respiratory failure, leading to hypoxaemia (PaO 2 <60 mmHg (8.0 kPa)), hypercapnia /

I C 

(PaCO2 >50 mmHg (6.65 kPa)) and acidosis (pH <7.35), cannot be managed non-invasively. 

 

AHF acute heart failure; BiPAP bilevel positive airway pressure; COPD chronic obstructive pulmonary disease; CPAP continuous positive airway pressure; PaCO2
"

partial pressure of carbon dioxide in arterial blood; PaO2 partial pressure of oxygen in arterial blood; SpO2 transcutaneous oxygen saturation. $

a
Class of recommendation.
%

 &

b
Level of evidence. '

&

c (

Reference(s) supporting recommendations. )

In AHF, oxygen should not be used routinely in non-hypoxaemic pa- mortality rates,543 although data regarding mortality are less
tients, as it causes vasoconstriction and a reduction in cardiac out- conclusive. CPAP is a feasible technique in the pre-hospital
put.546,547 In COPD, hyperoxygenation may increase ventilation setting, because it is simpler than pressure support positive
perfusion mismatch, suppressing ventilation and leading to hyper- end-expiratory pressure (PS-PEEP) and requires minimal training
capnia. During oxygen therapy, acid base balance and transcutane- and equipment. On hospital arrival, patients who still show signs
ous SpO2 should be monitored. of respiratory distress should continue with non-invasive ventila-
Non-invasive positive pressure ventilation includes both CPAP tion, preferably PS-PEEP, in case of acidosis and hypercapnia, par-
and bi-level positive pressure ventilation (PPV). Bi-level PPV also al- ticularly in those with a previous history of COPD or signs of
lows inspiratory pressure support that improves minute ventilation fatigue.540
and is especially useful in patients with hypercapnia, most typically Caution should be exercised with regard to side effects of anaes-
COPD patients. thetic drugs, among which propofol can induce hypotension and
Congestion affects lung function and increases intrapulmonary have cardiodepressive side effects. In contrast, midazolam may
shunting, resulting in hypoxaemia. The fraction of inspired oxygen have fewer cardiac side effects and thus is preferred in patients
(FiO2) should be increased up to 100% if necessary, according to with AHF or cardiogenic shock.
SpO2, unless contraindicated. Hyperoxia, however, should be A management algorithm for patients with AHF based on
avoided.546,547 Non-invasive positive pressure ventilation reduces the clinical profile during an early phase is presented in
respiratory distress541 545 and may decrease intubation and Figure 12.3.
Page 50 of 85 ESC Guidelines

"

"

"

- .

1 2

"

"

"

"

 

"

 &

'

&

Figure 12.3 Management of patients with acute heart failure based on clinical profile during an early phase
a
Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, an abnormal blood pressure re-
sponse to the Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites,
and peripheral oedema (right-sided).
ESC Guidelines Page 51 of 85

Pharmacological therapy

Recommendations for the management of patients with acute heart failure: pharmacotherapy

Recommendations Class a Level b Ref c


Diuretics

improve symptoms. It is recommended to regularly monitor symptoms, urine output, renal function and electrolytes during I C
use of i.v. diuretics.
In patients with new-onset AHF or those with chronic, decompensated HF not receiving oral diuretics the initial
recommended dose should be 2040 mg i.v. furosemide (or equivalent); for those on chronic diuretic therapy, initial i.v. I B 540, 548
dose should be at least equivalent to oral dose.
It is recommended to give diuretics either as intermittent boluses or as a continuous infusion, and the dose and duration
I B 548
should be adjusted according to patients symptoms and clinical status.
Combination of loop diuretic with either thiazide-type diuretic or spironolactone may be considered in patients with
IIb C 549

Vasodilators 7

"

i.v. vasodilators should be considered for symptomatic relief in AHF with SBP >90 mmHg (and without symptomatic
8

537, #

hypotension). IIa B
6

"

550555 %

Symptoms and blood pressure should be monitored frequently during administration of i.v. vasodilators. 5

In patients with hypertensive AHF, i.v. vasodilators should be considered as initial therapy to improve symptoms and reduce 537, "

IIa B
9

congestion. 551554 ,

- .

Inotropic agents dobutamine, dopamine, levosimendan, phosphodiesterase III (PDE III) inhibitors /

Short-term, i.v. infusion of inotropic agents may be considered in patients with hypotension (SBP <90 mmHg) and/or signs/
,

IIb C 1
0

peripheral perfusion and maintain end-organ function. "

"

An intravenous infusion of levosimendan or a PDE III inhibitor may be considered to reverse the effect of beta-blockade 0

IIb C
5

if beta-blockade is thought to be contributing to hypotension with subsequent hypoperfusion. "

Inotropic agents are not recommended unless the patient is symptomatically hypotensive or hypoperfused because of %

III A 556, 557


6

safety concern. "

Vasopressors 


A vasopressor (norepinephrine preferably) may be considered in patients who have cardiogenic shock, despite treatment
 

IIb B 558 

with another inotrope, to increase blood pressure and vital organ perfusion. !

"

It is recommended to monitor ECG and blood pressure when using inotropic agents and vasopressors, as they can cause 540,
I C
$

arrhythmia, myocardial ischaemia, and in the case of levosimendan and PDE III inhibitors also hypotension. 559563 
%

&

In such cases intra-arterial blood pressure measurement may be considered. IIb C (


'

&

Thrombo-embolism prophylaxis
)

Thrombo-embolism prophylaxis (e.g. with LMWH) is recommended in patients not already anticoagulated and with no
I B 564
contra-indication to anticoagulation, to reduce the risk of deep venous thrombosis and pulmonary embolism.
Other drugs

d
IIa C
b. amiodarone may be considered. IIb B 565567
Opiates may be considered for cautious use to relieve dyspnoea and anxiety in patients with severe dyspnoea but nausea
IIb B 568, 569
and hypopnea may occur.

AHF acute heart failure; ECG electrocardiogram; HF heart failure; i.v. intravenous; LMWH low molecular weight heparin; SBP systolic blood pressure.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
d
Beta-blockers should be used cautiously, if the patient is hypotensive.
Page 52 of 85 ESC Guidelines

Diuretics Use of an inotrope (Table 12.5) should be reserved for patients


Diuretics are a cornerstone in the treatment of patients with AHF with a severe reduction in cardiac output resulting in compromised
and signs of fluid overload and congestion. Diuretics increase renal vital organ perfusion, which occurs most often in hypotensive AHF.
salt and water excretion and have some vasodilatory effect. In pa- Inotropic agents are not recommended in cases of hypotensive AHF
tients with AHF and signs of hypoperfusion, diuretics should be where the underlying cause is hypovolaemia or other potentially
avoided before adequate perfusion is attained. correctable factors before elimination of these causes. Levosimen-
The initial approach to congestion management involves i.v. dan is preferable over dobutamine to reverse the effect of beta-
diuretics with the addition of vasodilators for dyspnoea relief if blockade if beta-blockade is thought to be contributing to hypoper-
blood pressure allows. To enhance diuresis or overcome diuretic fusion.572 However, levosimendan is a vasodilator, thus it is not suit-
resistance, options include dual nephron blockade by loop diuretics able for treatment of patients with hypotension (SBP ,85 mmHg)
(i.e. furosemide or torasemide) with thiazide diuretics or natriuretic or cardiogenic shock unless in combination with other inotropes or
doses of MRAs.570,571 However, this combination requires careful vasopressors.559,573,574 Inotropes, especially those with adrenergic
monitoring to avoid hypokalaemia, renal dysfunction and mechanisms, can cause sinus tachycardia and may induce myocardial
hypovolaemia. ischaemia and arrhythmias, thus ECG monitoring is required. There
Data defining optimal dosing, timing and method of delivery are in- is long-standing concern that they may increase mortality, which
complete. In the high-dose arm of the DOSE study, administration of
furosemide at 2.5 times the previous oral dose resulted in greater im-
provement in dyspnoea, larger weight change and fluid loss at the cost Table 12.5 Positive inotropes and/or vasopressors
7

of transient worsening in renal function.548 In AHF, i.v. furosemide is


"

used to treat acute heart failure #

the most commonly used first-line diuretic. The dose should be lim-
6

"

ited to the smallest amount to provide adequate clinical effect and Vasodilator Bolus Infusion rate


modified according to previous renal function and previous dose of 0

"

Dobutaminea No 220 g/kg/min (beta+) 9

diuretics. The initial i.v. dose should be at least equal to the pre- ,

Dopamine No 35 g/kg/min; inotropic (beta+) !

existing oral dose used at home. Consequently, patients with new-


- .

>5 g/kg/min: (beta+),


/

onset AHF or those with chronic HF without a history of renal failure




vasopressor (alpha+) 0

and previous use of diuretics may respond to i.v. boluses of 20 a,b




Milrinone 2575 g/kg 0.3750.75 g/kg/min 0

40 mg, whereas those with previous use of diuretics usually require


!

1 2

over 1020 min "

higher doses. A bolus of 1020 mg i.v. torasemide may be considered 4

Enoximonea
"

0.51.0 mg/kg 520 g/kg/min 0

as an alternative.
5

over 510 min


1

"

a
Levosimendan 12 g/kg over 0.1 g/kg/min, which can be
#

Vasodilators
6

10 min (optional) decreased to 0.05 or increased 2

"

c
to 0.2 g/kg/min
0

Intravenous vasodilators (Table 12.4) are the second most often 

used agents in AHF for symptomatic relief; however, there is no ro- Norepinephrine No 0.21.0 g/kg/min 

 

bust evidence confirming their beneficial effects. Epinephrine Bolus: 1 mg 0.050.5 g/kg/min 

can be given
!

They have dual benefit by decreasing venous tone (to optimize "

i.v. during
#

preload) and arterial tone (decrease afterload). Consequently,


$

resuscitation, %

they may also increase stroke volume. Vasodilators are especially


 &

repeated every '

useful in patients with hypertensive AHF, whereas in those with 35 min


&

SBP ,90 mmHg (or with symptomatic hypotension) they should *

be avoided. Dosing should be carefully controlled to avoid excessive i.v. intravenous.


a
Also a vasodilator.
decreases in blood pressure, which is related to poor outcome. Va- b
Not recommended in acutely worsened ischaemic heart failure.
sodilators should be used with caution in patients with significant c
Bolus not recommended in hypotensive patients.
mitral or aortic stenosis.

Table 12.4 Intravenous vasodilators used to treat acute heart failure

Vasodilator Dosing Main side effects Other


Nitroglycerine Start with1020 g/min, increase up to 200 g/min Hypotension, headache Tolerance on continuous use
Isosorbide dinitrate Start with 1 mg/h, increase up to 10 mg/h Hypotension, headache Tolerance on continuous use
Nitroprusside Start with 0.3 g/kg/min and increase up to 5 g/kg/min Hypotension, isocyanate toxicity Light sensitive
Nesiritidea Bolus 2 g/kg + infusion 0.01 g/kg/min Hypotension

a
Not available in many European countries.
ESC Guidelines Page 53 of 85

derives from studies in which intermittent or continuous infusions Device therapy


of inotropes were given.559 563,575 In any case, inotropes have to
be used with caution starting from rather low doses and up-titrating Recommendations regarding renal replacement
with close monitoring. therapy in patients with acute heart failure

Vasopressors Recommendations Class a Level b Ref C


Drugs with prominent peripheral arterial vasoconstrictor action
such as norepinephrine or dopamine in higher doses (.5 mg/kg/ patients with refractory congestion,
IIb B 578580
min) are given to patients with marked hypotension. These agents who failed to respond to diuretic-
based strategies.
are given to raise blood pressure and redistribute blood to the vital
organs. However, this is at the expense of an increase in LV Renal replacement therapy should
be considered in patients with
afterload. IIa C
refractory volume overload and
Dopamine was compared with norepinephrine in the treatment acute kidney injury.
of various shock patients. A subgroup analysis suggested that nor-
epinephrine would have fewer side effects and lower mortality.558 a
Class of recommendation.
Epinephrine (adrenaline) should be restricted to patients with per- b
Level of evidence.
c
sistent hypotension despite adequate cardiac filling pressures and Reference(s) supporting recommendations.

the use of other vasoactive agents, as well as for resuscitation 7

protocols.576
"

Renal replacement therapy 8

Ultrafiltration involves the removal of plasma water across a


6

"

Thromboembolism prophylaxis semipermeable membrane in response to a transmembrane pres- 

Thromboembolism prophylaxis with heparin or another anticoagu- sure gradient. There is no evidence favouring ultrafiltration over 0

"

lant is recommended unless contraindicated or unnecessary (be- loop diuretics as first-line therapy in patients with AHF.571,578 At ,

cause of existing treatment with oral anticoagulants). the present time, routine use of ultrafiltration is not recommended
- .

and should be confined to patients who fail to respond to diuretic-




Digoxin based strategies. 

Digoxin is mostly indicated in patients with AF and rapid ventricular The following criteria may indicate the need for initiation of renal
!

1 2

"

rate (.110 bpm) and given in boluses of 0.250.5 mg i.v. if not used replacement therapy in patients with refractory volume overload: 4

"

previously (0.06250.125 mg may be an adequate dose in patients


5

oliguria unresponsive to fluid resuscitation measures, severe hyper- 1

"

with moderate to severe renal dysfunction). However, in patients kalaemia (K+ .6.5 mmol/L), severe acidaemia (pH ,7.2), serum 0

with co-morbidities or other factors affecting digoxin metabolism urea level .25 mmol/L (150 mg/dL) and serum creatinine .300
6

"

(including other drugs) and/or the elderly, the maintenance dose mmol/L (.3.4 mg/dL). 

may be difficult to estimate theoretically, and in this situation it 

 

should be established empirically, based on the measurements of di- Mechanical assist devices 

goxin concentration in peripheral blood. Intra-aortic balloon pump "

The conventional indications for an intra-aortic balloon pump


$

 &

Vasopressin antagonists (IABP) are to support the circulation before surgical correction of '

Vasopressin antagonists such as tolvaptan block the action of argin-


&

specific acute mechanical problems (e.g. interventricular septal rup- (

ine vasopressin (AVP) at the V2 receptor in renal tubules and pro- ture and acute mitral regurgitation), during severe acute myocarditis *

mote aquaresis. Tolvaptan may be used to treat patients with and in selected patients with acute myocardial ischaemia or infarc-
volume overload and resistant hyponatraemia (thirst and dehydra- tion before, during and after percutaneous or surgical revasculariza-
tion are recognized adverse effects).577 tion. There is no good evidence that an IABP is of benefit in other
causes of cardiogenic shock (for details see below).
Opiates Ventricular assist devices
Opiates relieve dyspnoea and anxiety. In AHF, routine use of Ventricular assist devices and other forms of mechanical circulatory
opiates is not recommended and they may only be cautiously con- support (MCS) may be used as a bridge to decision or longer term
sidered in patients with severe dyspnoea, mostly with pulmonary in selected patients (see Section 13).
oedema. Dose-dependent side effects include nausea, hypotension,
bradycardia and respiratory depression (potentially increasing the Other interventions
need for invasive ventilation). There are controversies regarding In patients with AHF and pleural effusion, pleurocentesis with fluid
the potentially elevated mortality risk in patients receiving evacuation may be considered if feasible in order to alleviate
morphine.568,569 dyspnoea.
In patients with ascites, ascitic paracentesis with fluid evacuation
Anxiolytics and sedatives may be considered in order to alleviate symptoms. This procedure,
Anxiolytics or sedatives may be needed in a patient with agitation or through reduction in intra-abdominal pressure, may also partially
delirium. Cautious use of benzodiazepines (diazepam or lorazepam) normalize the transrenal pressure gradient, thus improving renal
may be the safest approach. filtration.581
Page 54 of 85 ESC Guidelines

12.3.4 Management of patients with cardiogenic shock 12.4 Management of evidence-based oral
Cardiogenic shock is defined as hypotension (SBP ,90 mmHg) des- therapies
pite adequate filling status with signs of hypoperfusion (Table 12.2).
The pathogenetic scenarios of cardiogenic shock range from low- Recommendations regarding oral evidence-based
output advanced end-stage chronic HF to acute-onset de novo disease-modifying therapies in patients with acute heart
cardiogenic shock most often caused by STEMI, but also by various failure
aetiologies other than ACS. A patient in cardiogenic shock should
undergo immediate comprehensive assessment. ECG and echocar-
Recommendations Class a Level b
diography are required immediately in all patients with suspected
cardiogenic shock. In patients with cardiogenic shock complicating In case of worsening of chronic HFrEF, every
attempt should be made to continue evidence-
ACS, an immediate coronary angiography is recommended (within based, disease-modifying therapies, in the I C
2 h from hospital admission) with an intent to perform coronary absence of haemodynamic instability or contra-
revascularization.114,535 Invasive monitoring with an arterial line indications.
should be also considered. In the case of de novo HFrEF, every attempt
There is no agreement on the optimal method of haemodynamic should be made to initiate these therapies after I C
monitoring in assessing and treating patients in cardiogenic shock, haemodynamic stabilization.
including pulmonary artery catheterization.
Pharmacologic therapy aims to improve organ perfusion by increas- AHF acute heart failure; HFrEF heart failure with reduced ejection 7

fraction. "

ing cardiac output and blood pressure. After fluid challenge, pharmaco- a
Class of recommendation.
8

logic management consists of an inotropic agent and a vasopressor as


6

b
Level of evidence.
"

needed. Treatment is guided by the continuous monitoring of organ 

perfusion and haemodynamics. Pulmonary artery catheterization may 0

"

be considered. As a vasopressor, norepinephrine is recommended ,

Oral disease-modifying HF therapy should be continued on ad-


!

when mean arterial pressure needs pharmacologic support. Dobuta-


- .

mission with AHF, except in the presence of haemodynamic in-




mine is the most commonly used adrenergic inotrope. Levosimendan




may also be used in combination with a vasopressor.582,583 Levosimen-


,

stability (symptomatic hypotension, hypoperfusion, bradycardia), 

dan infusion in cardiogenic shock following AMI on top of dobutamine hyperkalaemia or severely impaired renal function. In these cases,
!

1 2

"

and norepinephrine improved cardiovascular haemodynamics without the daily dosage of oral therapy may be reduced or stopped tem- 4

"

leading to hypotension.582,583 PDE3 inhibitors may be another option, porarily until the patient is stabilized. In particular, beta-blockers
5

"

especially in non-ischaemic patients.561,584 can be safely continued during AHF presentations except in car- 0

However, rather than combining several inotropes, device therapy has diogenic shock. A recent meta-analysis demonstrated that discon- 6

"

tinuation of beta-blockers in patients hospitalized with AHF was


0

to be considered when there is an inadequate response. Recently the 

IABP-SHOCK II trial showed that the use of an IABP did not improve associated with significantly increased in-hospital mortality, short- 

 

outcomes in patients suffering from AMI and cardiogenic shock.585,586 term mortality and the combined endpoint of short-term rehos- 

pitalization or mortality.587
!

Therefore, routine use of an IABP cannot be recommended. "

Recommendations regarding management of patients with cardiogenic shock  &

'

&

Recommendations Class a Level b Ref c *

In all patients with suspected cardiogenic shock, immediate ECG and echocardiography are recommended. I C
All patients with cardiogenic shock should be rapidly transferred to a tertiary care center which has a 24/7 service of cardiac
I C
catheterization, and a dedicated ICU/CCU with availability of short-term mechanical circulatory support.
In patients with cardiogenic shock complicating ACS an immediate coronary angiography is recommended (within 2 hours
I C
from hospital admission) with an intent to perform coronary revascularization.
Continous ECG and blood pressure monitoring are recommended. I C
Invasive monitoring with an arterial line is recommended. I C

I C

Intravenous inotropic agents (dobutamine) may be considered to increase cardiac output. IIb C
Vasopressors (norepinephrine preferable over dopamine) may be considered if there is a need to maintain SBP in the
IIb B 558
presence of persistent hypoperfusion.
IABP is not routinely recommended in cardiogenic shock. III B 585, 586
Short-term mechanical circulatory support may be considered in refractory cardiogenic shock depending on patient age,
IIb C
comorbidities and neurological function.

ACS acute coronary syndrome; CCU coronary care unit; ECG electrocardiogram; IABP intra-aortic balloon pump; ICU intensive care unit; SBP systolic blood
pressure.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
ESC Guidelines Page 55 of 85

12.5 Monitoring of clinical status of once provided with tailored education and advice about self-care.
patients hospitalized due to acute heart Patients should preferably be
failure enrolled in a disease management programme; follow-up plans
must be in place prior to discharge and clearly communicated
Recommendations regarding monitoring of clinical to the primary care team;
status of patients hospitalized due to acute heart failure reviewed by their general practitioner within 1 week of discharge;
seen by the hospital cardiology team within 2 weeks of discharge
Recommendations Class a Level b if feasible.
Standard non-invasive monitoring of heart rate,
rhythm, respiratory rate, oxygen saturation and I C Patients with chronic HF should be followed up within a multipro-
blood pressure is recommended. fessional HF service. Pre- and post-discharge management should
It is recommended that patients should be follow the standards of care of the HFA.540,591,592
I C
chart completed.
12.7 Goals of treatment during the
It is recommended to evaluate signs and
symptoms relevant to HF (e.g. dyspnoea, different stages of management of acute
I C
pulmonary rales, peripheral oedema, weight) heart failure
During the treatment of patients with AHF, one can distinguish
V

Frequent, often daily,measurement of


W

subsequent stages that require different therapeutic approaches B

renal function (blood urea, creatinine) and U

electrolytes (potassium, sodium) during (described in the previous sections of this chapter). Importantly, D

I C
>

i.v. therapy and when renin-angiotensin- the goals of treatment during the different stages of management T

aldosterone system antagonists are initiated is of patients with AHF also differ, and are summarized in
A

recommended. Table 12.6.


K

L M

Intra-arterial line should be considered in N

>

patients with hypotension and persistent IIa C O

symptoms despite treatment. >

Pulmonary artery catheter may be considered


P Q

Table 12.6 Goals of treatment in acute heart failure A

in patients who, despite pharmacological


R

treatment present refractory symptoms IIb C P


O

(particularly with hypotension and Immediate (ED/ICU/CCU) A=

hypoperfusion). Improve haemodynamics and organ perfusion.


B

Q?

Restore oxygenation. <


O

HF heart failure; i.v. intravenous. N

a
Class of recommendation. Alleviate symptoms. ;

< =

b
Level of evidence. Limit cardiac and renal damage. >

Prevent thrombo-embolism.
A

Patients should be weighed daily and an accurate fluid balance chart


C

Minimize ICU length of stay. ;


D

should be maintained. Renal function should preferably be moni-


Intermediate (in hospital) F

tored with daily measurement of BUN/urea, creatinine and electro- G

Identify aetiology and relevant co-morbidities.


H

lytes. Routine use of a urinary catheter is not recommended. I

Renal function is commonly impaired at admission, but may im- Titrate therapy to control symptoms and congestion and optimize blood
pressure.
prove or deteriorate with diuresis. Routine monitoring of pulse, re-
spiratory rate and blood pressure should continue. There is no Initiate and up-titrate disease-modifying pharmacological therapy.
study showing the usefulness of invasive haemodynamic monitoring Consider device therapy in appropriate patients.
in patients with AHF excluding those with cardiogenic shock. There Pre-discharge and long-term management
is evidence that measuring NPs during the hospital admission may Develop a careplan that provides:
help with discharge planning. Patients whose NP concentrations o A schedule for up-titration and monitoring of pharmacological therapy.
fall during admission have lower cardiovascular mortality and re- o Need and timing for review for device therapy.
admission rates at 6 months.588 590 o Who will see the patient for follow-up and when.
Enrol in disease management programme, educate, and initiate
12.6 Criteria for discharge from hospital appropriate lifestyle adjustments.
and follow-up in high-risk period Prevent early readmission.
552 Improve symptoms, quality of life, and survival.
Patients admitted with AHF are medically fit for discharge
when haemodynamically stable, euvolaemic, established on
CCU coronary care unit; ED emergency department; ICU intensive care
evidence-based oral medication and with stable renal function unit.
for at least 24 hours before discharge;
Page 56 of 85 ESC Guidelines

13. Mechanical circulatory support for patients receiving ECMO for refractory cardiogenic shock
(online calculator at http://www.save-score.com).594
and heart transplantation In addition, MCS systems, particularly ECLS and ECMO, can be
used as a bridge to decision (BTD) in patients with acute and rap-
13.1 Mechanical circulatory support idly deteriorating HF or cardiogenic shock to stabilize haemo-
For patients with either chronic or acute HF who cannot be stabi- dynamics, recover end-organ function and allow for a full clinical
lized with medical therapy, MCS systems can be used to unload the evaluation for the possibility of either heart transplant or a more
failing ventricle and maintain sufficient end-organ perfusion. Patients durable MCS device.595
in acute cardiogenic shock are initially treated with short-term as- Evidence regarding the benefits of temporary percutaneous MCS
sistance using extracorporeal, non-durable life support systems so in patients not responding to standard therapy, including inotropes,
that more definitive therapy may be planned. Patients with chronic, is limited. In a meta-analysis of three randomized clinical trials
refractory HF despite medical therapy can be treated with a per- comparing a percutaneous MCS vs. IABP in a total of 100 patients
manent implantable left ventricular assist device (LVAD). Table 13.1 in cardiogenic shock, percutaneous MCS appeared safe and demon-
lists the current indications for the use of mechanical circulatory as- strated better haemodynamics, but did not improve 30-day mortal-
sist devices.593 ity and was associated with more bleeding complications.596 In a
randomized trial on high-risk PCI in patients with impaired LV func-
tion (PROTECT II trial), the 30-day incidence of major adverse
13.1.1 Mechanical circulatory support in acute heart events was not different for patients with IABP or a haemodynamic V

failure
support device.597 Based on these results, temporary percutaneous
A

To manage patients with AHF or cardiogenic shock (INTERMACS


B

MCS cannot be recommended as a proven or efficacious treatment


U

level 1), short-term mechanical support systems, including percu- T

for acute cardiogenic shock. In selected patients it may serve as a >

taneous cardiac support devices, extracorporeal life support S

bridge to definite therapy. A difficult decision to withdraw MCS O

(ECLS) and extracorporeal membrane oxygenation (ECMO) may X

may need to be made when the patient has no potential for cardiac K

be used to support patients with left or biventricular failure until @

recovery and is not eligible for longer-term MCS support or heart


L M

cardiac and other organ function have recovered. Typically the


N

transplant.
>

use of these devices is restricted to a few days to weeks. The Survival


O

>

After Veno-arterial ECMO (SAVE) score can help to predict survival O

13.1.2 Mechanical circulatory support in end-stage chronic


P Q

heart failure S

Heart transplantation has always been a limited therapeutic option P

A=

Table 13.1 Terms describing various indications for for patients with end-stage chronic HF. The increasing number of O

mechanical circulatory support patients with refractory, chronic HF and the declining willingness
U

Q?

for organ donation have resulted in expanded waiting lists and pro- <

Bridge to Use of short-term MCS (e.g. ECLS or ECMO) longed waiting times for patients listed for heart transplantation ;

decision (BTD)/ in patients with cardiogenic shock until


< =

haemodynamics and end-organ perfusion are


(median 16 months in the region covered by Eurotransplant).598 >

Bridge to ?

bridge (BTB) stabilized, contra-indications for long-term MCS More than 60% of patients are transplanted in high-urgency status, A

are excluded (brain damage after resuscitation) leaving little chance for patients listed for less urgent transplantation.
C

and additional therapeutic options including ; E

Three times more patients are listed for heart transplantation annu-
long-term VAD therapy or heart transplant can F

be evaluated. ally than are actually transplanted, and the mortality rate on the G

Eurotransplant waiting list in 2013 was 21.7%.598


H

Bridge to Use of MCS (usually LVAD) to improve end-organ J

candidacy function in order to make an ineligible patient More recent data suggest that patients with ongoing LVAD sup-
(BTC) eligible for heart transplantation. port may have an improved survival on the transplant waiting
Bridge to Use of MCS (LVAD or BiVAD) to keep patient list.599 Accordingly, MCS devices, particularly continuous-flow
transplantation alive who is otherwise at high risk of death before LVADs, are increasingly seen as an alternative to heart transplant-
(BTT) transplantation until a donor organ becomes
available. ation. Initially LVADs were developed for use as a short-term BTT
Bridge to Use of MCS (typically LVAD) to keep patient approach (Table 13.1),600 but they are now being used for months
recovery (BTR) to years in patients who will either face a long-term wait on the
remove MCS. transplant list (currently only 10% of patients with an MCS device
Destination Long-term use of MCS (LVAD) as an alternative implanted with a BTT indication will receive an organ within 1
therapy (DT) to transplantation in patients with end-stage HF year of listing) or in patients who are not eligible for transplantation
ineligible for transplantation or long-term waiting
for heart transplantation. as permanent therapy or destination therapy. The number of pa-
tients with a permanent LVAD who are considered neither too
BiVAD biventricular assist device; BTB bridge to bridge; BTC bridge to
old nor ineligible for transplantation is constantly growing. For a ma-
candidacy; BTD bridge to decision; BTR bridge to recovery; BTT bridge to jority of these patients, lifelong LVAD therapy, despite eligibility for
transplantation; DT destination therapy; ECLS extracorporeal life support; transplantation, has become a clinical reality. Current 23-year sur-
ECMO extracorporeal membrane oxygenation; HF heart failure; LVAD
left ventricular assist device; MCS mechanical circulatory support; VAD
vival rates in carefully selected patients receiving the latest continu-
ventricular assist device. ous flow devices are excellent, and comparable to early survival
after heart transplantation.595 However, fewer data are available
ESC Guidelines Page 57 of 85

Table 13.2 INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) stages for classifying
patients with advanced heart failure

INTERMACS level NYHA Description Device 1y survival with


Class LVAD therapy
1. Cardiogenic shock IV Haemodynamic instability in spite of increasing doses of catecholamines ECLS, ECMO, 52.65.6%
Crash and burn and/or mechanical circulatory support with critical hypoperfusion of target percutaneous
organs (severe cardiogenic shock). support devices
2. Progressive decline IV Intravenous inotropic support with acceptable blood pressure but rapid ECLS, ECMO, 63.13.1%
despite inotropic deterioration of renal function, nutritional state, or signs of congestion. LVAD
support Sliding on
inotropes
3. Stable but inotrope IV Haemodynamic stability with low or intermediate doses of inotropics, but LVAD 78.42.5%
dependent Dependent necessary due to hypotension, worsening of symptoms, or progressive
stability renal failure.
4. Resting symptoms IV Temporary cessation of inotropic treatment is possible, but patient presents LVAD 78.73.0%
ambulatory
5. Exertion intolerant IV Complete cessation of physical activity, stable at rest, but frequently with LVAD 93.03.9%a V

Housebound ambulatory A

6. Exertion limited III Minor limitation on physical activity and absence of congestion while at LVAD / Discuss -
B

Walking wounded rest. Easily fatigued by light activity. LVAD as option D

>

7. Placeholder III Discuss LVAD - S

as option
A

L M

ECLS extracorporeal life support; ECMO extracorporeal membrane oxygenation; INTERMACS Interagency Registry for Mechanically Assisted Circulatory Support; N

>

LVAD left ventricular assist device; NYHA New York Heart Association. O

a
K

Kaplan-Meier estimates with standard error of the mean for 1 year survival with LVAD therapy. Patients were censored at time of last contact, recovery or heart transplantation. >

Due to small numbers outcomes for INTERMACS levels 5, 6, 7 were combined610.


O

P Q

A=

for longer-term outcomes. Among patients with continuous-flow INTERMACS class, although the majority of VAD implants are O

LVADs, actuarial survival is 80% at 1 year and 70% at 2 years in pre- done at INTERMACS levels 1 3.604,610 Additionally, it needs to
U

Q?

dominantly non-transplant-eligible patients. Notably, survival of be remembered that no RCTs exist comparing medical therapy <

85% at 2 years was recorded for patients up to 70 years of age with- vs. MCS devices in these transplant-eligible patients (Table 13.2). ;

< =

out diabetes, renal impairment or cardiogenic shock.601,602 Patients Typically, patients with end-stage HF considered for MCS exhibit >

many clinical hallmarks of declining cardiovascular function593 and


@

receiving LVAD devices as BTT have a post-transplant survival rate A

similar or better than those not requiring or receiving bridging.599 may already be on continuous inotropic support or manifest a de-
C

; E

Despite technological improvements, bleeding, thromboembolism cline in end-organ function. Markers of liver and renal dysfunction, F

(both of which can cause stroke), pump thrombosis, driveline infec- haematologic and coagulation abnormalities and lower serum albu- G

min levels are associated with worse outcome.611,612


H

tions and device failure remain significant problems and affect the I

long-term outcome of patients on MCS. 599,603 606 It is recom- Evaluation of RV function is crucial since postoperative RV failure
mended that such devices should only be implanted and managed greatly increases perioperative mortality and reduces survival to,
at centres with appropriately trained specialist HF physicians and and after, transplantation. There are, however, multiple approaches
surgeons and an outpatient LVAD clinic with trained nursing staff.607 to assessment of the RV (see Section 5.2.3). If RV failure is expected
In some patients, LV reverse remodelling and functional improve- to be potentially reversible, temporary (days to weeks) extracor-
ment during MCS may permit removal of the LVAD [bridge to re- poreal right ventricular assist device (RVAD) support using a centri-
covery (BTR)]. This outcome is more likely in younger patients with fugal pump in addition to LVAD implantation may be considered.
an acute fulminant but reversible cause of HF, such as acute myocar- For patients with chronic biventricular failure or a high risk for per-
ditis or peripartum cardiomyopathy.608,609 LVADs may also be used sisting RV failure after LVAD implantation, implantation of a biven-
as a bridge to candidacy (BTC) in order to permit recovery of tricular assist device (BiVAD) may be necessary. Patients requiring
end-organ dysfunction, improve RV function and relieve pulmonary long-term BiVAD support must be transplant-eligible, as BiVAD
hypertension, which may allow initially ineligible patients to become therapy is not suitable for destination therapy. The outcomes of Bi-
eligible for heart transplantation. VAD therapy are inferior to those for LVAD therapy and therefore
Earlier ventricular assist device (VAD) implantation in less severe- the indication for VAD therapy should be discussed before RV func-
ly ill patients, e.g. those not yet on inotropic support, was tested in a tion deteriorates. The implantation of a total artificial heart with re-
recent trial that revealed better outcomes than in those patients moval of the native heart should be restricted to selected patients
continuing on medical therapy.605 The INTERMACS registry like- who cannot be treated with an LVAD (unrepairable ventricular sep-
wise shows better outcomes in patients implanted with a higher tal defect, cardiac rupture).
Page 58 of 85 ESC Guidelines

Table 13.3 Patients potentially eligible for Table 13.4 Heart transplantation: indications and
implantation of a left ventricular assist device contra-indications

Patients with >2 months of severe symptoms despite optimal Patients to End-stage HF with severe symptoms, a poor prognosis,
medical and device therapy and more than one of the following: consider and no remaining alternative treatment options.
Motivated, well informed, and emotionally stable.
LVEF <25% and, if measured, peak VO2 <12 mL/kg/min.
Capable of complying with the intensive treatment
3 HF hospitalizations in previous 12 months without an obvious required postoperatively.
precipitating cause.
Contra- Active infection.
Dependence on i.v. inotropic therapy. indications Severe peripheral arterial or cerebrovascular disease.
Progressive end-organ dysfunction (worsening renal and/or hepatic Pharmacologically irreversible pulmonary hypertension
(LVAD should be considered with a subsequent re-
pressure (PCWP 20 mmHg and SBP 8090 mmHg or CI 2 L/min/m2). evaluation to establish candidacy).
Cancer (a collaboration with oncology specialists
Absence of severe right ventricular dysfunction together with severe should occur to stratify each patient as to their risk of
tricuspid regurgitation. tumour recurrence).
Irreversible renal dysfunction (e.g. creatinine clearance
<30 mL/min).
CI cardiac index; HF heart failure; i.v. intravenous; LVEF left ventricular
Systemic disease with multi-organ involvement.
ejection fraction; PCWP pulmonary capillary wedge pressure; SBP systolic
blood pressure; VO2 oxygen consumption.
Other serious co-morbidity with poor prognosis. V

Pre-transplant BMI >35 kg/m2 (weight loss is A

recommended to achieve a BMI <35 kg/m2). B

Current alcohol or drug abuse. D

Any patient for whom social supports are deemed


>

Patients with active infection, severe renal, pulmonary or hepatic


T

dysfunction or uncertain neurological status after cardiac arrest or


A

setting.
X

due to cardiogenic shock are not usually candidates for BTT or


K

L M

DT but may be candidates for BTC (Table 13.3). BMI body mass index; HF heart failure; LVAD left ventricular assist device.
N

>

>

P Q

Recommendations for implantation of mechanical A

circulatory support in patients with refractory heart


S

13.2 Heart transplantation


O

failure
P

A=

Heart transplantation is an accepted treatment for end-stage


O

HF.614,615 Although controlled trials have never been conducted,


U

Q?

a b c
Recommendations Class Level Ref A

there is a consensus that transplantationprovided that proper se-


<

An LVAD should be considered in :

lection criteria are appliedsignificantly increases survival, exercise


;

patients who have end- stage HFrEF < =

despite optimal medical and device capacity, quality of life and return to work compared with conven- >

therapy and who are eligible for tional treatment. A

heart transplantation in order IIa C Apart from the shortage of donor hearts, the main challenges in
C

to improve symptoms, reduce the


D

; E

risk of HF hospitalization and the transplantation are the consequences of the limited effectiveness F

and complications of immunosuppressive therapy in the long term


G

risk of premature death (Bridge to H

transplant indication). (i.e. antibody-mediated rejection, infection, hypertension, renal fail- I

An LVAD should be considered in ure, malignancy and coronary artery vasculopathy). The indications
patients who have end-stage HFrEF for and contraindications to heart transplantation have recently
despite optimal medical and device 605, 612, been updated and are summarized in Table 13.4.616 It needs to be
IIa B
therapy and who are not eligible for 613
heart transplantation to, reduce the considered that some contraindications are transient and treatable.
risk of premature death. While an active infection remains a relative contraindication to heart
transplantation, patients with HIV, hepatitis, Chagas disease and tu-
HF heart failure; HFrEF heart failure with reduced ejection fraction; LVAD berculosis can be considered as suitable candidates provided certain
left ventricular assist device. strict management principles are adhered to by the teams. In pa-
a
Class of recommendation.
b tients with cancer requiring heart transplantation, a close collabor-
Level of evidence.
c
Reference(s) supporting levels of evidence. ation with oncology specialists should occur to stratify each patient
as to their risk of tumour recurrence.616
ESC Guidelines Page 59 of 85

Table 14.1 Characteristics and components of Recommendations for exercise, multidisciplinary


management programmes for patients with heart management and monitoring of patients with heart
failure failure

Characteristics Should employ a multidisciplinary approach Recommendations Class a Level b Ref c


(cardiologists, primary care physicians, nurses,
pharmacists, physiotherapists, dieticians, social It is recommended that regular
workers, surgeons, psychologists, etc.). aerobic exercise is encouraged 321,
I A
in patients with HF to improve 618621
Should target high-risk symptomatic patients. functional capacity and symptoms.
Should include competent and professionally It is recommended that regular
educated staff.617 aerobic exercise is encouraged in
I A 618, 619
Components Optimized medical and device management. stable patients with HFrEF to reduce
the risk of HF hospitalization.
Adequate patient education, with special emphasis
on adherence and self-care. It is recommended that patients with
HF are enrolled in a multidisciplinary
Patient involvement in symptom monitoring and care management programme to I A 622625
reduce the risk of HF hospitalization
Follow-up after discharge (regular clinic and/or and mortality.
home-based visits; possibly telephone support or
V

Referral to primary care for long- A

remote monitoring).
W

term follow-up may be considered B

for stable HF patients who are on


A

Increased access to healthcare (through in-person IIb B 626, 627


D

follow-up and by telephone contact; possibly optimal therapy to monitor for >

through remote monitoring). effectiveness of treatment, disease S

progression and patient adherence. X

Facilitated access to care during episodes of K

decompensation. Monitoring of pulmonary artery L


@

pressures using a wireless


N

>

Assessment of (and appropriate intervention in implantable haemodynamic O

response to) an unexplained change in weight,


K

monitoring system (CardioMems)


>

nutritional status, functional status, quality of life, may be considered in symptomatic IIb B 628, 629 P
O

patients with HF with previous


R

Access to advanced treatment options. HF hospitalization in order to P


O

reduce the risk of recurrent HF A=

Provision of psychosocial support to patients and


hospitalization.
O

family and/or caregivers. D

Q?

Multiparameter monitoring based A

on ICD (IN-TIME approach) may be


<

considered in symptomatic patients IIb B 630 ;

< =

with HFrEF (LVEF 35%) in order to >

improve clinical outcomes. ?

HF heart failure; HFrEF heart failure with reduced ejection fraction; ICD
D

; E

The use of mechanical circulatory support, particularly LVAD, implantable cardioverter-defibrillator; LVEF left ventricular ejection fraction, F

should be considered for patients with potentially reversible or IN-TIME Implant-based multiparameter telemonitoring of patients with heart failure.
G

a
H

Class of recommendation.
treatable co-morbidities, such as cancer, obesity, renal failure,
I

b
Level of evidence.
tobacco use and pharmacologically irreversible pulmonary c
Reference(s) supporting levels of evidence.
hypertension, with a subsequent re-evaluation to establish
candidacy.
14.1 Organization of care
The goal of management of HF is to provide a seamless system of
14. Multidisciplinary team care that embraces both the community and hospital throughout
the health care journey. The standards of care that patients with HF
management should expect have been published by the ESC HFA.591 To achieve
Non-pharmacological non-device/surgical interventions used in the this goal, other services, such as cardiac rehabilitation and palliative
management of HF (both HFrEF and HFpEF) are summarized in care, must be integrated into the overall provision for patients with
Tables 14.1 and 14.2 and detailed practical recommendations on HF. Fundamental to the delivery of this complete package of care
their use have been published by the HFA of the ESC.591,592 There are multidisciplinary management programmes designed to improve
is no evidence that these on their own improve mortality, morbidity outcomes through structured follow-up with patient education, opti-
or quality of life. For this reason, these interventions have not been mization of medical treatment, psychosocial support and improved
given a recommendation with an evidence level. The exceptions are access to care (Table 14.1). Such strategies reduce HF hospitalization
implementation of care in a multidisciplinary framework, monitoring and mortality in patients discharged from the hospital.624,625
and exercise training (see recommendations table), all of which are Key to the success of these programmes is coordination of care
discussed below. along the continuum of HF and throughout the chain of care
Page 60 of 85 ESC Guidelines

Table 14.2 Key topics and self-care skills to include in patient education and the professional behaviours to optimize
learning and facilitate shared decision making

Education topic Patient skills Professional behaviours


Understand the cause of HF, symptoms and disease Provide oral and written information that takes account of educational
aetiology and trajectory. grade and health literacy.
trajectory of Make realistic decisions including decisions about Recognize HF disease barriers to communication and provide
HF (including treatment at end-of-life. information at regular time intervals.
prognosis). Sensitively communicate information on prognosis at time of diagnosis,
during decision making about treatment options, when there is a
change in the clinical condition and whenever the patient requests.
Symptom Monitor and recognize change in signs and symptoms. Provide individualized information to support self-management such as:
monitoring and Know how and when to contact a healthcare professional. _ In the case of increasing dyspnoea or oedema or a sudden
self-care. In line with professional advice, know when to self- unexpected weight gain of >2 kg in 3 days, patients may increase
their diuretic dose and/or alert their healthcare team.
_
_ Self-care support aids such as dosette box when appropriate.
Pharmacological Understand the indications, dosing and side effects of drugs. Provide written and oral information on dosing, effects and side
treatment. Recognize the common side effects and know effects (see web tables 7.47.8 practical guidance on use of
when to notify a healthcare professional. pharmacological agents).
V

Implanted devices Understand the indications and aims of procedures/ W

and percutaneous/ implanted devices. Provide written and oral information on regular control of device U

surgical Recognize the common complications and know when to functioning, along with documentation of regular check-up.
D

interventions. notify a healthcare professional.


>

implanted devices. X

Immunization Advise on local guidance and immunization practice.


@

L M

disease N

>

Diet and alcohol O

weight and periods of high heat and humidity. Adjust advice during
>

_ Increase intake during periods of high heat and periods of acute decompensation and consider altering these P
@

humidity, nausea/vomiting restrictions towards end-of-life. R

_ Fluid restriction of 1.52 L/day may be considered in Tailor alcohol advice to aetiology of HF; e.g. abstinence in A

patients with severe HF to relieve symptoms and alcoholic cardiomyopathy. P

A=

congestion. Normal alcohol guidelines apply (2 units per day in men or 1 unit per O

Monitor body weight and prevent malnutrition. day in women). 1 unit is 10 mL of pure alcohol (e.g. 1 glass of wine, 1/2 D

Eat healthily, avoid excessive salt intake (>6 g/day) and pint of beer, 1 measure of spirit).
Q?

maintain a healthy body weight. For management of obesity (see Section 11.15).
O

<

Abstain from or avoid excessive alcohol intake, especially ;


:

for alcohol induced cardiomyopathy. < =

>

Smoking and Stop smoking and taking recreational substances. Refer for specialist advice for smoking cessation and drug withdrawal ?

recreational and replacement therapy. A

substance use. Consider referral for cognitive behavioural theory and psychological C

support if patient wishes support to stop smoking. ;


D

Exercise Advice on exercise that recognizes physical and functional limitations, G


F

moderate breathlessness. such as frailty, comorbidities. H

Referral to exercise programme when appropriate. I

Travel and leisure Prepare travel and leisure activities according to physical
capacity.

Be aware of adverse reactions to sun exposure with


certain medication (such as amiodarone).
Consider effect of high altitude on oxygenation.
take medicine in cabin luggage in the plane, have a list with
you of treatments and the dosage with the generic name.
Sleep and Recognize problems with sleeping, their relationship with Provide advice such as timing of diuretics, environment for sleep, device
breathing (see HF and how to optimize sleep. support.
co-morbidities In presence of sleep-disordered breathing provide advice on weight
Section 11.16). reduction/control.
Sexual activity (see Be reassured about engaging in sex, provided sexual Provide advice on eliminating factors predisposing to erectile
co-morbidities activity does not provoke undue symptoms. dysfunction and available pharmacological treatment of erectile
Section 11.7). Recognize problems with sexual activity, their relationship dysfunction.
with HF and applied treatment and how to treat erectile Refer to specialist for sexual counselling when necessary.
dysfunction.

continued
ESC Guidelines Page 61 of 85

Table 14.2 Key topics and self-care skills to include in patient education and the professional behaviours to optimize
learning and facilitate shared decision making (continued)

Education topic Patient skills Professional behaviours


Psychosocial Understand that depressive symptoms and cognitive Regularly communicate information on disease, treatment options and
aspects dysfunction are found more frequently in people with HF, self-management.
and that they may affect adherence. Involve family and carers in HF management and self-care.
Recognize psychological problems which may occur Refer to specialist for psychological support when necessary.
in the course of disease, in relation to changed lifestyle,
pharmacotherapy, implanted devices and other
procedures (including mechanical support and heart
transplantation).

HF heart failure; ICD implantable cardioverter defibrillator.

delivered by the various services within the health care system. This exercise tolerance, health-related quality of life and HF hospitaliza-
necessitates close collaboration between HF practitioners (primar- tion rates in patients with HF. A single large RCT618 showed a modest
ily cardiologists, HF nurses and general practitioners) and other ex- and non-significant reduction in the primary composite outcome of
perts, including pharmacists, dieticians, physiotherapists, all-cause mortality or all-cause hospitalization. There was no reduc- V

psychologists, palliative care providers and social workers. The con- tion in mortality and no safety concerns were raised.618,633 The W

most recent Cochrane review of exercise training619 included 33


U

tent and structure of HF management programmes may vary in dif- A

ferent countries and health care settings. The components shown in trials with 4740 patients with HF (predominantly HFrEF). There
>

Table 14.1 are recommended. HF services should be easily access- was a trend towards a reduction in mortality with exercise in trials
O

ible to the patient and his/her family and care providers. A telephone with .1 year of follow-up. Compared with the control group, exer- K

helpline may facilitate access to professional advice. cise training reduced the rate of overall and HF-specific hospitaliza-
L M

>

The website http://ww.heartfailurematters.org is an option for tion and improved quality of life. Practical recommendations on O

professional information for those patients and families with Inter- exercise training have been published by the HFA.120 >

net access. There is evidence that in patients with HFpEF, exercise training has
P Q

several benefits, including improvements in exercise capacity, as mea- S

14.2 Discharge planning


A

sured objectively using peak oxygen consumption, quality of life and P

A=

Early readmission after hospital discharge is common and may be ad- diastolic function, assessed by echocardiography.321,620,621,634 O

dressed through coordinated discharge planning. The standards of


D

Patients with HF, regardless of LVEF, are recommended to perform


U

Q?

care that patients should expect have been published by the HFA properly designed exercise training (see the recommendations table). <
O

and the Acute Cardiac Care Association.540,631 Discharge planning ;


:

should commence as soon as the patients condition is stable. During 14.5 Follow-up and monitoring
< =

>

hospital admission, providing patients with information and education


?

Patients with HF benefit from regular follow-up and monitoring of A

for self-care improves outcome. Discharge should be arranged for biomedical parameters to ensure the safety and optimal dosing of
C

when the patient is euvolaemic and any precipitants of the admission


D

; E

medicines and detect the development of complications or disease


have been treated. Hospitals with early physician follow-up after dis- progression that may require a change in management (e.g. the onset G
F

charge show reduced 30-day readmission, and those that initiated of AF or development of anaemia). Monitoring may be undertaken by
H

programmes to discharge patients with an outpatient follow-up ap- the patients themselves during home visits, in community or hospital
pointment already scheduled experienced a greater reduction in clinics, by remote monitoring with or without implanted devices or
readmissions than those not taking up this strategy.632 by structured telephone support (STS). The optimal method of mon-
itoring will depend on local organizations and resources and will vary
14.3 Lifestyle advice among patients. For example, more frequent monitoring will be re-
There is little evidence that specific lifestyle advice improves quality quired during periods of instability or optimization of medication.
of life or prognosis; however, providing this information has become Older adults may also benefit from more frequent monitoring.
a key component of education for self-care. Patients should be pro- Some patients will be keen and able to participate in self-monitoring.
vided with sufficient up-to-date information to make decisions on High circulating NPs predict unfavourable outcomes in patients
lifestyle adjustment and self-care. Ideally for those patients admitted with HF, and a decrease in NP levels during recovery from circula-
to the hospital, lifestyle advice should begin prior to discharge. Infor- tory decompensation is associated with a better prognosis.588 590
mation should be individually tailored to need and take into account Although it is plausible to monitor clinical status and tailor treatment
relevant co-morbidities that may influence retention of information based on changes in circulating NPs in patients with HF, published
(such as cognitive impairment and depression). Practical recommen- studies have provided differing results.635 638 This does not enable
dations have been published by the HFA.591 Key topics to include us to recommend a broad application of such an approach.
are recommended in Table 14.2. Telemedicine in HF, which is also termed remote patient manage-
ment, has variable clinical trial results.639 Several meta-analyses sug-
14.4 Exercise training gest clinical benefits, but numerous prospectively initiated clinical
Several systematic reviews and meta-analyses of small studies have trials including .3700 patients have not confirmed this. These clin-
shown that physical conditioning by exercise training improves ical trials include Tele-HF,640 TIM-HF,641 INH,642 WISH643 and
Page 62 of 85 ESC Guidelines

TEHAF.644 It is clear that there is not just one type of telemedicine,


and each approach needs to be assessed on its individual merit. Table 14.3 Specific recommendations regarding
Recently, two individual approaches were shown to be successful monitoring and follow-up of the older adult with heart
in improving clinical outcome when used in patients with HFpEF or failure
HFrEF. These approaches include the CardioMems system (tested
Monitor frailty and seek and address reversible causes (cardiovascular
in 550 patients with both HFrEF and HFpEF)628 and the IN-TIME
and non-cardiovascular) of deterioration in frailty score.
approach (tested in 664 HFrEF patients)630, which may be considered
Medication review: optimize doses of heart failure medication slowly and
for use in selected patients with HF (see the recommendations table).
with frequent monitoring of clinical status. Reduce polypharmacy; number,
doses and complexity of regime. Consider stopping medication without an
14.6 The older adult, frailty and cognitive immediate effect on symptom relief or quality of life (such as statin). Review
the timing and dose of diuretic therapy to reduce risk of incontinence.
impairment
Consider need to refer to specialist care of the elderly team and to
HF management and self-care behaviour are complicated by ageing, general practitioner and social worker, etc. for follow-up and support for
co-morbid conditions, cognitive impairment, frailty and limited so- the patient and his/her family.
cial support. HF is also a leading cause of hospital admission in the
older adult, where it is associated with increased hospital length of
stay and risk of mortality.645
Frailty is common in older adults with HF, with a recent study sug-
Table 14.4 Patients with heart failure in whom end of V

gesting it may be present in .70% of patients with HF and .80 A

life care should be considered


W

years of age.645 Frailty scoring systems provide an objective assess-


B

ment and identify the presence of or change in the level of frailty. T

Progressive functional decline (physical and mental) and dependence in


>

Patients with a high frailty score will benefit from closer contact most activities of daily living.
S

with the HF specialist team, more frequent follow-up and monitor- X

Severe heart failure symptoms with poor quality of life despite optimal K

ing and individualized self-care support. pharmacological and non-pharmacological therapies. L


@

Frailty scores include646 walking speed (gait speed test), timed


N

>

Frequent admissions to hospital or other serious episodes of


up-and-go test, PRISMA 7 questionnaire, Frail Score,647 Fried
O

decompensation despite optimal treatment.


K

>

Score647,648 and Short Physical Performance Battery (SPPB).


D

Heart transplantation and mechanical circulatory support ruled out.


@

P Q

Cognitive impairment and HF frequently coexist. Acute delirium R

Cardiac cachexia.
S

is also associated with decompensated HF and may be present on P


O

hospital admission. Cognitive function can be assessed using the Clinically judged to be close to end of life. A=

Mini-Mental State Examination649 or the Montreal cognitive assess- D

Q?

ment.650 The presence of delirium and HF is found more commonly


A

<

in older adults and is associated with increased mortality and poorer ;


:

self-care ability and increases any hospital length of stay.651 There is


< =

Table 14.5 Key components of palliative care service >

currently no clinical evidence that HF medication worsens or im-


?

in patients with heart failure


@

proves cognitive function. However, its effect on HF outcome


B

suggests such medication should be used. Support from a multidis-


D

Focus on improving or maintaining the quality of life of a patient and his/


; E

ciplinary HF team in collaboration with specialist dementia support her family as well as possible until he/she dies. G
F

teams, alongside medication compliance aids, tailored self-care Frequent assessment of symptoms (including dyspnoea and pain)
H

advice and involvement of family and caregivers, may improve resulting from advanced heart failure and other co-morbidities and focus
adherence with complex HF medication and self-care regimens on symptom relief.
(see Table 14.2 on patient education) (Table 14.3). Access for the patient and his/her family to psychological support and
spiritual care according to need.

14.7 Palliative and end-of-life care Advanced care planning, taking account of preferences for place of
death and resuscitation (which may include deactivating devices, such as
Palliative care approaches include a focus on symptom management,
emotional support and communication between the patient and his/
her family. Ideally this should be introduced early in the disease trajec-
tory and increased as the disease progresses. A decision to alter the
focus of care from modifying disease progression to optimising quality approach, is required in order to address and optimally coordinate
of life should be made in discussion with the patient, cardiologist, the patients care. Recent pilot studies have suggested an improve-
nurse and general practitioner. The patients family should be involved ment in symptom burden and quality of life,653,655 but these data are
in such discussions if requested by the patient652,653 (Table 14.4). too limited to provide a recommendation.
Key components of a palliative care service are recommended in Specific therapies and actions may provide palliation of symptoms
Table 14.5. Palliative care has been discussed in detail in a position and improve quality of life but have a limited evidence base:
paper from the ESC HFA.654
Liaison between the specialist palliative care services and the HF Morphine (with an antiemetic when high doses are needed) can
team and/or the primary care physician, using a shared care be used to reduce breathlessness, pain and anxiety.656
ESC Guidelines Page 63 of 85

Increasing the inspired oxygen concentration may provide relief Targeted therapies for specific aetiologies of HFrEF (e.g. myo-
of dyspnoea. carditis, peripartum cardiomyopathy)
Diuretic management can be used to relieve severe congestion Therapies directly improving cardiomyocyte function (e.g.
or optimize symptom control (congestion and thirst). acto-myosin cross-bridge activation, sarco/endoplasmic re-
Reduce HF drugs that reduce blood pressure to maintain suffi- ticulum Ca2+-ATPase activation, ryanodine receptor stabiliza-
cient oxygenation and reduce the risk of falls. tion, energetic modulation) or targeting non-myocytic
compartment (e.g. anti-fibrosis/matrix remodelling)
Ideally these therapies should be delivered in the patients home. In the
Therapies for HFmrEF/HFpEF (ARNIs, beta-blockers, soluble
majority of cases the whole family should receive social support.652
guanyl cyclase inhibitors, i.v. iron)
A management plan should be developed through discussion with
the patient and family. It should include 4. Devices and interventions
A discussion about stopping medication that does not have an im- Indications for ICDs in specific subgroups (e.g. ARVC and
mediate effect on symptom management or health-related quality HFmrEF/HFpEF) and optimal selection of ICD candidates
of life, such as agents to lower cholesterol or treat osteoporosis QRS morphology or duration as a predictor of response to CRT
Documentation of the patients decision regarding resuscitation CRT in patients with AF
attempts Efficacy of PV ablation as a rhythm-control strategy in patients
Deactivation of an ICD at end-of-life (according to local legal with AF
regulations) Interventional approach to recurrent, life-threatening ven- V

Preferred place for care and death tricular tachyarrhythmias


W

Emotional support to the patient and family/caregiver with ap-


U

The role of remote monitoring strategies in HF


A

propriate referral for psychological or spiritual support Non-surgical (percutaneous) correction of functional mitral
>

and tricuspid regurgitations


O

Clearly, symptoms and quality of life change over time and regular
A

reassessment is recommended. Palliative scores provide an object- Identification of indications for coronary angiography/revascu- K

L M

ive assessment of the patients symptoms and needs and may help larization in patients with HF and chronic stable CAD N

>

establish the effectiveness of therapy. Effects of novel LVADs as destination therapy and bridge to O

transplantation
>

Palliative outcome scores include the Palliative Care Outcome


D

P Q

Scale,657 Karnofsky Performance Status658 and Functional Assess- 5. Co-morbidities


A

ment of Chronic Illness Therapy Palliative Care (FACIT-Pal).659


S

A better understanding of pathophysiology and potential A=

treatments in specific HF populations, including the


B

Q?

very elderly,
A

15. Gaps in evidence young patients,


<
O

Clinicians responsible for managing patients with HF must frequently eGFR ,30 mL/min, < =

>

make treatment decisions without adequate evidence or a consensus diabetic patients, ?

of expert opinion. The following is a short list of selected, common cardiotoxic chemotherapy-induced HF,
B

issues that deserve to be addressed in future clinical research. muscular dystrophies, ;


D

cachexia and depression. G


F

1. Definition, diagnosis, epidemiology Therapies for HF-related sleep-disordered breathing in HFrEF/ H

HFpEF/HFmrEF.
J

For HFmrEF/HFpEF, research into the underlying characteris-


tics, pathophysiology and diagnosis (with new modalities) 6. Acute heart failure
Updated epidemiology on HF incidence and prevalence includ-
ing patients from all continents Prospective evaluation of the time-to-treatment concept in AHF
For imaging and biomarkers, studies on effects of specific im- Evaluation of whether inadequate phenotyping is responsible
aging modalities and biomarkers to improve clinical outcome for the failure of treatments to improve outcome in AHF
(e.g. biomarker-guided therapies, detection of CAD/myocardial Better definition and treatment of diuretic resistance
ischaemia, late-gadolinium enhancement CMR, echocardio- Role of nitrates in the management of AHF
graphic strain measurements, stress echocardiography, etc.) Treatments improving mortality and morbidity
Increasing awareness of HF in the medical community, lay pub- Strategies and therapies to prevent early rehospitalization after
lic and among policy makers. discharge for a hospital admission for AHF.

2. Strategies aimed at prevention and screening of HF 7. Other/remaining aspects

Evaluate the comparative clinical effectiveness and cost- Treatment algorithms for patients with HF excluded by pivotal
effectiveness of different strategies to screen for HF. clinical trials
Palliative and end-of-life care management and assessment of
3. Pharmacological therapy
outcome
Identification of non-responders to current guideline-advised Optimal integration of multidisciplinary care, self-management
medical treatment of patients and their adherence.
Page 64 of 85 ESC Guidelines

16. To do and not to do messages from the Guidelines

Recommendations for cardiac imaging in patients with suspected or established heart failure Class a Level b
TTE is recommended for the assessment of myocardial structure and function in subjects with suspected HF in order to establish a
I C
diagnosis of either HFrEF, HFmrEF or HFpEF.
TTE is recommended for the assessment of LVEF in order to identify patients with HF who would be suitable for evidence-based
I C
pharmacological and device (ICD, CRT) treatment recommended for HFrEF.
Recommendations aiming to prevent or delay the development of overt heart failure or prevent death Class a Level b
before the onset of symptoms
Treatment of hypertension is recommended to prevent or delay the onset of HF and prolong life. I A
ACE-I is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction in order to
I A
prevent or delay the onset of HF and prolong life.
Beta-blocker is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction, in order
I B
to prevent or delay the onset of HF and prolong life.
Pharmacological treatments indicated in patients with symptomatic heart failure with reduced ejection Class a Level b
V

fraction
W

An ACE-Ic is recommended, in addition to a beta-blocker, for symptomatic patients with HFrEF to reduce the risk of HF D

I A
T

>

hospitalization and death. T

A beta-blocker is recommended, in addition to an ACE-Ic, for patients with stable, symptomatic HFrEF to reduce the risk of HF X

I A
hospitalization and death. K

L M

c
An MRA is recommended for patients with HFrEF, who remain symptomatic despite treatment with an ACE-I and a beta-blocker, to
N

I A
=

>

reduce the risk of HF hospitalization and death. O

>

a b
Other pharmacological treatments recommended in selected patients with symptomatic heart failure with Class Level P
O

reduced ejection fraction


A

Diuretics are recommended in order to improve symptoms and exercise capacity in patients with signs and/or symptoms of congestion. I B
O

A=

Sacubitril/valsartan is recommended as a replacement for an ACE-I to further reduce the risk of HF hospitalization and death in O

I B D

ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRA. U

Q?

Treatments (or combinations of treatments) that may cause harm in patients with symptomatic (New York Class a Level b
<

Heart Association Class IIIV) heart failure with reduced ejection fraction ;

< =

Diltiazem or verapamil are not recommended in patients with HFrEF, as they increase the risk of HF worsening and HF hospitalization. III C >

The addition of an ARB (or a renin inhibitor) to the combination of an ACE-I and an MRA is not recommended in patients with HF, B

III C C

because of the increased risk of renal dysfunction and hyperkalaemia. ;


D

a b
Class Level G
F

Secondary prevention
H

An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients who have recovered from a ventricular I A
arrhythmia causing haemodynamic instability, and who are expected to survive for >1 year with good functional status.
Primary prevention
An ICD is recommended to reduce the risk of sudden death and all-cause mortality in patients with symptomatic HF (NYHA Class
IIIII), and an LVEF 35% despite 3 months of OMT, provided they are expected to survive substantially longer than 1 year with good
functional status, and they have:
IHD (unless they have had an MI in the prior 40 days) I A
DCM I B
ICD implantation is not recommended within 40 days of an MI as implantation at this time does not improve prognosis. III A
a
Recommendations for cardiac resynchronization therapy implantation in patients with heart failure Class Level b

CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration 150 msec and LBBB QRS morphology and
I A
with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration of 130149 msec and LBBB QRS
I B
morphology and with LVEF 35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA Class who have an indication for ventricular
I A

CRT is contra-indicated in patients with a QRS duration <130 msec III A

continued
ESC Guidelines Page 65 of 85

To do and not to do messages from the Guidelines (continued)

Not-recommended treatments of co-morbidities in patients with heart failure Class a Level b

Adaptive servo-ventilation is not recommended in patients with HFrEF and a predominant central sleep apnoea because of an
III B
increased all-cause and cardiovascular mortality.

Thiazolidinediones (glitazones) are not recommended in patients with HF, as they increase the risk of HF worsening and HF hospitalization. III A

NSAIDs or COX-2 inhibitors are not recommended in patients with HF, as they increase the risk of HF worsening and HF hospitalization. III B

Recommendations regarding diagnostic measurements in patients with suspected acute heart failure Class a Level b

Upon presentation a measurement of plasma natriuretic peptide level (BNP, NT-proBNP or MR-proANP) is recommended in all
I A
patients with acute dyspnoea and suspected AHF to help in the differentiation of AHF from non-cardiac causes of acute dyspnoea.

Recommendations for the management of patients with acute heart failure pharmacotherapy Class a Level b

I C
symptoms. It is recommended to regularly monitor symptoms, urine output, renal function and electrolytes during use of i.v. diuretics.
In patients with new-onset AHF or those with chronic, decompensated HF not receiving oral diuretics the initial recommended dose
should be 2040 mg i.v. furosemide (or equivalent); for those on chronic diuretic therapy, initial i.v. dose should be at least equivalent to I B V

oral dose. A

It is recommended to give diuretics either as intermittent boluses or a continuous infusion, and the dose and duration should be
U

I B D

adjusted according to the patients symptoms and clinical status.


T

>

Inotropic agents are not recommended unless the patient is symptomatically hypotensive or hypoperfused because of safety concern. III A O

a b
Recommendations regarding management of patients with cardiogenic shock Class Level
K

L M

In all patients with suspected cardiogenic shock, immediate ECG and echocardiography are recommended. I C N

>

All patients with cardiogenic shock should be rapidly transferred to a tertiary care centre which has a 24/7 service of cardiac >

I C
D

catheterization, and a dedicated ICU/CCU with availability of short-term mechanical circulatory support.
O

P Q

Recommendations regarding oral evidence-based disease-modifying therapies in patients with acute heart failure Class a Level b
S

In case of worsening of chronic HFrEF, every attempt should be made to continue evidence-based, disease-modifying therapies, in the
A=

I C O

absence of haemodynamic instability or contra-indications. B

Q?

a b
Recommendations for exercise, multidisciplinary management, and monitoring of patients with heart failure Class Level
A

<

It is recommended that regular aerobic exercise is encouraged in patients with HF to improve functional capacity and symptoms. I A ;

< =

It is recommended that regular aerobic exercise is encouraged in stable patients with HFrEF to reduce the risk of HF hospitalization. I A >

It is recommended that patients with HF are enrolled in a multidisciplinary care management programme to reduce the risk of HF B

I A C

hospitalization and mortality. ;


D

ACE-I angiotensin-converting enzyme inhibitor; AHF acute heart failure;; ARB angiotensin receptor blocker; AST aspartate aminotransferase; AV atrio-ventricular; H

BNP B-type natriuretic peptide; CCU coronary care unit; COX-2 cyclooxygenase 2; CRT cardiac resynchronization therapy; CT computed tomography; DCM J

dilated cardiomyopathy; ECG electrocardiogram; HF heart failure; HFmrEF heart failure with mid-range ejection fraction; HFpEF heart failure with preserved ejection
fraction; HFrEF heart failure with reduced ejection fraction; ICD implantable cardioverter-defibrillator; ICU intensive care unit; i.v. intravenous; LBBB left bundle
branch block; LV left ventricular; LVEF left ventricular ejection fraction; MI myocardial infarction; MRA mineralocorticoid receptor antagonist; MR-proANP mid-
regional pro A-type natriuretic peptide; NSAIDs non-steroidal anti-inflammatory drugs; NT-proBNP N-terminal pro-B type natriuretic peptide; NYHA New York Heart
Association; OMT optimal medical therapy; QRS Q, R, and S waves (combination of three of the graphical deflections); RV right ventricular; TTE transthoracic
echocardiography.
a
Class of recommendation.
b
Level of evidence
c
Or ARB if ACEI is not tolerated/contra-indicated.

17. Web Addenda


All Web figures and Web tables are available in the Web addenda, available at European Heart Journal online and also via the ESC website.
Page 66 of 85 ESC Guidelines

18. Appendix Aladashvili; Germany: German Cardiac Society, Andreas Luchner;


Greece: Hellenic Cardiological Society, Christina Chrysohoou;
ESC Committee for Practice Guidelines (CPG): Jose Luis Za- Hungary: Hungarian Society of Cardiology, Noemi Nyolczas; Ice-
morano (Chairperson) (Spain), Victor Aboyans (France), Stephan land: Icelandic Society of Cardiology, Gestur Thorgeirsson; Israel:
Achenbach (Germany), Stefan Agewall (Norway), Lina Badimon Israel Heart Society, Jean Marc Weinstein; Italy: Italian Federation
(Spain), Gonzalo Baron-Esquivias (Spain), Helmut Baumgartner of Cardiology, Andrea Di Lenarda; Kazakhstan: Association of
(Germany), Jeroen J. Bax (The Netherlands), Hector Bueno (Spain), Cardiologists of Kazakhstan, Nazipa Aidargaliyeva; Kosovo: Kosovo
Scipione Carerj (Italy), Veronica Dean (France), etin Erol (Turkey), Society of Cardiology, Gani Bajraktari; Kyrgyzstan: Kyrgyz Society
Donna Fitzsimons (UK), Oliver Gaemperli (Switzerland), Paulus of Cardiology, Medet Beishenkulov; Latvia: Latvian Society of Car-
Kirchhof (UK/Germany), Philippe Kolh (Belgium), Patrizio Lancellot- diology, Ginta Kamzola; Lebanon: Lebanese Society of Cardiology,
ti (Belgium), Gregory Y. H. Lip (UK), Petros Nihoyannopoulos (UK), Tony Abdel-Massih; Lithuania: Lithuanian Society of Cardiology,
Massimo F. Piepoli (Italy), Piotr Ponikowski (Poland), Marco Roffi Jelena Celutkiene; Luxembourg: Luxembourg Society of Cardi-
(Switzerland), Adam Torbicki (Poland), Antonio Vaz Carneiro (Por- ology, Stephanie Noppe; Malta: Maltese Cardiac Society, Andrew
tugal), Stephan Windecker (Switzerland). Cassar; Moldova: Moldavian Society of Cardiology, Eleonora Vata-
ESC National Cardiac Societies actively involved in the re- man; Morocco: Moroccan Society of Cardiology, Saadia Abir-
view process of the 2016 ESC Guidelines for the diagnosis and treat- Khalil; The Netherlands: Netherlands Society of Cardiology, Pet-
ment of acute and chronic heart failure ra van Pol; Norway: Norwegian Society of Cardiology, Rune Mo;
Armenia: Armenian Cardiologists Association, Hamayak Poland: Polish Cardiac Society, Ewa Straburzynska-Migaj; Portu- V

S. Sisakian; Azerbaijan: Azerbaijan Society of Cardiology, Elnur


A

gal: Portuguese Society of Cardiology, Candida Fonseca; Romania: W

Isayev; Belarus: Belorussian Scientific Society of Cardiologists, Ale- Romanian Society of Cardiology, Ovidiu Chioncel; Russian Feder-
U

na Kurlianskaya; Belgium: Belgian Society of Cardiology, Wilfried


T

ation: Russian Society of Cardiology, Evgeny Shlyakhto; San Mar- >

Mullens; Bulgaria: Bulgarian Society of Cardiology, Mariya Tokma- ino: San Marino Society of Cardiology, Marco Zavatta; Serbia:
S

kova; Cyprus: Cyprus Society of Cardiology, Petros Agathangelou; Cardiology Society of Serbia, Petar Otasevic; Slovakia: Slovak So- K

Czech Republic: Czech Society of Cardiology, Vojtech Melenovs-


@

ciety of Cardiology, Eva Goncalvesova; Slovenia: Slovenian Society


L M

ky; Denmark: Danish Society of Cardiology, Henrik Wiggers; of Cardiology, Mitja Lainscak; Spain: Spanish Society of Cardiology,
=

>

Egypt: Egyptian Society of Cardiology, Mahmoud Hassanein; Es-


K

Beatriz Daz Molina; Sweden: Swedish Society of Cardiology, Maria >

tonia: Estonian Society of Cardiology, Tiina Uuetoa; Finland: Finn- Schaufelberger; Switzerland: Swiss Society of Cardiology, Thomas P
@

ish Cardiac Society, Jyri Lommi; Former Yugoslav Republic of


R

Suter; Turkey: Turkish Society of Cardiology, Mehmet Birhan S

Macedonia: Macedonian FYR Society of Cardiology, Elizabeta Srbi- Ylmaz; Ukraine: Ukrainian Association of Cardiology, Leonid Vor- P
T

A=

novska Kostovska; France: French Society of Cardiology, Yves Juil- onkov; United Kingdom: British Cardiovascular Society, Ceri O

liere; Georgia: Georgian Society of Cardiology, Alexander Davies.


U

Q?

<

< =

>

The CME text 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure is accredited by the European Board for Accreditation in Cardiology (EBAC). ?

EBAC works according to the quality standards of the European Accreditation Council for Continuing Medical Education (EACCME), which is an institution of the European Union of B

Medical Specialists (UEMS). In compliance with EBAC/EACCME Guidelines, all authors participating in this programme have disclosed any potential conflicts of interest that might cause
C

a bias in the article. The Organizing Committee is responsible for ensuring that all potential conflicts of interest relevant to the programme are declared to the participants prior to the ; E

CME activities. G
F

CME questions for this article are available at: European Heart Journal http://www.oxforde-learning.com/eurheartj and European Society of Cardiology http://www. H

escardio.org/guidelines I

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